It would be interesting to benchmark the alternatives...

What do you think of

@h{<QA>}=undef;
[download]

? It still uses more memory than iteration, since it creates the (potentially large) temporary array to index, but on the flipside it's likely faster than the iteration approach for sane-sized files, I think...

Edit: benchmarks:

Re-Edit: benchmarks for different array sizes, and added "undef @h{@data}", thanks [id://hdb]:

These benchmarks are in-memory only - no file access involved, since I wasn't sure how to make sure caching didn't impact the results without creating a whole bunch of temp files and making sure the disk cache was trashed.

They're also just for the "load the data into the hash" micro-step, not the whole "compute the difference" operation.

#!/usr/bin/perl

use strict;
use warnings;
use Benchmark qw(:all :hireswallclock);

foreach my $arraySize(10,100,1_000,10_000,100_000) {
    my @data=map rand,0..$arraySize;

    print "========== ARRAY SIZE: $arraySize\n";

    cmpthese(
            -1,
            {
                '@tmp=@arr' => sub {
                    my @arr = @data;
                    my %h;
                    @h{@arr} = @arr;
                },
                '@tmp=undef' => sub {
                    my @arr = @data;
                    my %h;
                    @h{@arr} = undef;
                },
                'loop=1' => sub {
                    my %h;
                    foreach (@data) {
                        $h{$_} = 1;
                    }
                },
                'loop=undef' => sub {
                    my %h;
                    foreach (@data) {
                        $h{$_} = undef;
                    }
                },
                '@h{@data}=1' => sub {
                    my %h;
                    @h{@data} = 1;
                },
                '@h{@data}=undef' => sub {
                    my %h;
                    @h{@data} = undef;
                },
                'undef @h{@data}' => sub {
                    my %h;
                    undef @h{@data};
                },
            }
        );
}
[download]

Results:

========== ARRAY SIZE: 10
                    Rate @tmp=@arr @tmp=undef loop=1 loop=undef @h{@data}=1 @h{@data}=undef undef @h{@data}
@tmp=@arr        49764/s        --       -33%   -54%       -55%        -64%            -66%            -67%
@tmp=undef       74467/s       50%         --   -31%       -33%        -46%            -48%            -51%
loop=1          107884/s      117%        45%     --        -3%        -22%            -25%            -28%
loop=undef      111002/s      123%        49%     3%         --        -20%            -23%            -26%
@h{@data}=1     138688/s      179%        86%    29%        25%          --             -4%             -8%
@h{@data}=undef 144398/s      190%        94%    34%        30%          4%              --             -4%
undef @h{@data} 150886/s      203%       103%    40%        36%          9%              4%              --
========== ARRAY SIZE: 100
                   Rate @tmp=@arr @tmp=undef loop=1 loop=undef @h{@data}=undef @h{@data}=1 undef @h{@data}
@tmp=@arr        5566/s        --       -36%   -57%       -57%            -65%        -66%            -66%
@tmp=undef       8660/s       56%         --   -33%       -34%            -45%        -46%            -47%
loop=1          12992/s      133%        50%     --        -0%            -18%        -20%            -20%
loop=undef      13035/s      134%        51%     0%         --            -17%        -19%            -20%
@h{@data}=undef 15754/s      183%        82%    21%        21%              --         -3%             -3%
@h{@data}=1     16162/s      190%        87%    24%        24%              3%          --             -0%
undef @h{@data} 16214/s      191%        87%    25%        24%              3%          0%              --
========== ARRAY SIZE: 1000
                  Rate @tmp=@arr @tmp=undef loop=1 loop=undef @h{@data}=undef undef @h{@data} @h{@data}=1
@tmp=@arr        534/s        --       -38%   -59%       -59%            -66%            -67%        -67%
@tmp=undef       860/s       61%         --   -34%       -35%            -45%            -46%        -46%
loop=1          1309/s      145%        52%     --        -1%            -16%            -18%        -18%
loop=undef      1316/s      147%        53%     1%         --            -15%            -18%        -18%
@h{@data}=undef 1555/s      191%        81%    19%        18%              --             -3%         -3%
undef @h{@data} 1601/s      200%        86%    22%        22%              3%              --          0%
@h{@data}=1     1601/s      200%        86%    22%        22%              3%              0%          --
========== ARRAY SIZE: 10000
                  Rate @tmp=@arr @tmp=undef loop=1 loop=undef @h{@data}=1 undef @h{@data} @h{@data}=undef
@tmp=@arr       51.5/s        --       -33%   -57%       -60%        -64%            -65%            -66%
@tmp=undef      77.3/s       50%         --   -36%       -40%        -45%            -48%            -49%
loop=1           121/s      135%        56%     --        -6%        -14%            -19%            -20%
loop=undef       128/s      149%        66%     6%         --         -9%            -14%            -15%
@h{@data}=1      141/s      175%        83%    17%        10%          --             -5%             -6%
undef @h{@data}  149/s      189%        93%    23%        16%          5%              --             -1%
@h{@data}=undef  151/s      193%        95%    25%        18%          7%              1%              --
========== ARRAY SIZE: 100000
                  Rate @tmp=@arr @tmp=undef loop=undef loop=1 @h{@data}=1 @h{@data}=undef undef @h{@data}
@tmp=@arr       3.72/s        --       -35%       -61%   -62%        -67%            -68%            -69%
@tmp=undef      5.74/s       54%         --       -39%   -41%        -49%            -51%            -51%
loop=undef      9.42/s      153%        64%         --    -4%        -17%            -20%            -20%
loop=1          9.80/s      164%        71%         4%     --        -13%            -16%            -17%
@h{@data}=1     11.3/s      204%        97%        20%    15%          --             -4%             -4%
@h{@data}=undef 11.7/s      216%       104%        25%    20%          4%              --             -1%
undef @h{@data} 11.8/s      218%       106%        26%    21%          5%              1%              --