Why not use a hash?

#!/usr/bin/perl -w

use strict;

my $html = <<END_OF_HTML;
Hello! oX
World!

<;<;<;<;

Hi!
Samn! (~)
END_OF_HTML

my %emotes = map {split /#####|\n/} <DATA>;

for my $entry(keys %emotes) {
        $html =~ s!\Q$entry\E!<img src="$emotes{$entry}.gif">!g;
}

print $html;

__DATA__
oX#####skullandbones
<;#####pie
(o)#####goatse
(~)#####ninja
[download]

Note that im removing the trailing newline in the split operation, which is -ew- ugly.