(the previous thread he mentions is "Pattern Matching", not using regex)

How many strings are you searching for? Is it just 2 or 3, or is it 200-300?

Can the match span lines in the big file? Like this, for instance:

...............AAAAAAAA"ATGGCTC
GTGTCCA"AAAAAAAAAAA ...........
[download]

That would obviously complicate things...

If you only have a manageable number of strings to match, and a match can't occur across lines, I'd suggest something like this (which does use regexes, but if you have multiple strings to match at once, I don't know how to avoid them easily):

use Regex::PreSuf;

sub superMatch {
    my ($patternFile, $dataFile, $outFile)=@_;
    open(PAT,"<$patternFile") or die "Can't open $patternFile, error $
+!";
    my @patterns=<PAT>;
    chomp @patterns;
    close(PAT);

    open(OUT, ">>$outFile") or die "Can't open output file $outFile, e
+rror $!";

    # Regex::PreSuf generates a regex that will match all
    # of the patterns much more quickly than a naive 
    # join "|",@patterns will
    my $re=presuf(@patterns);

    open(DATA,"<$dataFile") or die "Can't open $dataFile, error $!";
    # NO NEED TO READ INTO MEMORY ALL AT ONCE!
    while(<DATA>) {
        # only compile regex once
        if(/$re/o) {
           # only chomp if we have a match
           chomp;
           # capturing matches are slower, so only capture 
           # if one or more matches are present.
           # might have more than one match in a line!
           while(/($re)/og) {
               print OUT "'$1', '$_'";
           }
        }
    }
}
[download]

I haven't tested this, but it could be a start for you...
--
Mike