A hash seems reasonable to use at that dictionary size. 50k is nothing.

Nevertheless, if you're still concerned, I suggest you use grep with eq on the list of words, rather than trying to match a pattern against a long string. That is going to be a lot more efficient.

Something like this:

my %word;

open my $fh, "<", "/usr/dict/words";
chomp, push @{$word{substr $_, 0, 1}}, $_ while <$fh>;
close $fh;
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And then you check using something like:

if(grep $_ eq $user_input, @{$word{substr $user_input, 0, 1} || []}) {
    # it's there
}
else {
    # no, that wasn't it
}
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If you want to ignore case, you'd just use

chomp, $_ = lc, push @{$word{substr($_, 0, 1)}}, $_ while <$fh>;

# and

grep lc eq $user_input, @{$word{substr($user_input, 0, 1)} || []}
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respectively.

Makeshifts last the longest.