There are some unclear parts in your code, we don't know how your data looks like (so there may be any kind of problem).

You should alwyas open one file after another and do all the work in one file at once. I reorganized your code (out of the blue, don't know your data) - maybe thats a new starting point.

...
my $echo = 'ECHO';
my ($dffname, $listname) = @ARGV;
my $fh;

# read key/val lists
open $fh, '<', $dffname or die "$dffname $!";
my %lijst = map { chomp; (split /\t|\s{2,}/)[1,0] } <$fh>;
close $fh;

# readfile list
open $fh, '<', $listname or die "$listname $!";
my @listfiles = <$fh>; chomp @listfiles;
close $fh;

for my $file (@listfiles) {
   # read original file
   open $fh, '<', $file or die "$file $!";
   local $/;  my $content = <$fh>;
   close $fh;

   # modify content
   while( my ($key, $val) = each %lijst ) {
      next unless $val == 1;
      $content =~ s/^$key$/$echo/gms;
      $content =~ s/^$key$/$echo/;   # re-subsitute first (?)
   }
   # write modified file
   open $fh, '>', "$file.out" or die "$file.out $!";
   print $fh $content
}
...
[download]

Regards

mwa