Hello littlewenwen, and welcome to the Monastery!

Yes, you can do in-line updates using the standard Tie::File module:

#! perl
use strict;
use warnings;
use Tie::File;

my $filename = 'RawFile.txt';

tie my @lines, 'Tie::File', $filename or die "Cannot tie file '$filena
+me': $!";

for my $i (0 .. $#lines)
{
    my @fields = split /\t/, $lines[$i], -1;
    @fields = map { $_ eq '' ? 'Missing' : $_ } @fields;
    $lines[$i] = join("\t", @fields);
}

untie @lines;
[download]

Output in RawFile.txt:

abcd    123     456     defg
cdefg   23      Missing as
Missing 345     235     Missing
xsd     Missing swe     Missing
[download]

Hope that helps,

Update 1: Added -1 as LIMIT argument to split to get trailing empty fields.

Update 2: Added final “Missing” to output; the final tab was missing from my input file on line 4. Thanks to kcott for the heads-up.

Note, though, that Tie::File will probably have to rewrite the remainder of your file every time you change a line. It's clever, but probably not the right way to do what you want.