"I couldn't see any way to get an "E" with your test data, so I added some extra data to my test cases. In the future, it is best if you can provide an example "desired output" that demo's the basic decisions which need to be made.

ok. Please consider again the input files, with both candidates, for E and M as well. File 1

chr7    151046672
chr7    151047369
chr3    127680920
chr3    127680920
[download]

File 2

chr1    66953622    66953654
chr1    67200451    67200472
chr1    67200475    67200478
chr1    67058869    67058880
chr1    67058881    67058885
chr7    151046672    127680920
chr7    151047369    127680920
chr3    127680920    151046672
chr3    127680920    151047369
[download]

Code for now.

#!/usr/bin/perl
use warnings; 
use strict;
use Data::Dumper;

my $file1 = $ARGV[0];
open($infile1,$file1);
my $file2 = $ARGV[1];
open($infile2,$file2);

my %file2_hash;

while (my $line = <$infile1>)
{
   chomp $line;  #so that output with E or M can be on same line
   next if $line =~ /^\s*$/;   #skip blank lines (a common infile goof
+)
   
   my ($chr, $val1, $val2) = split /\s+/,$line;
}
close $infile1;

while (my $line = <$infile2>)
{
chomp $line;   
 next if $line =~ /^\s*$/;   #skip blank lines (a common infile goof)
   
   my ($key, $value1, $value2) = split /\s+/, $line; # use better "nam
+es" I have
                                           # no idea of what a chr col
   $file2_hash{"$key:$value1:$value2"} = 1;

  # file handle closure is optional, but I'd do it.

###  process each line in file2:
###  If a line "matches" with any line in file1, then "E", else "M"
###  I don't know that these numbers mean, come up with better comment

close $infile2;

   if (exists $file2_hash{"$chr:$val1:$val2"})
   {
      print "$line\tE\n";  # match exists with file 1   
}
   else
   {
   print "$line\tM\n";  # match does NOT exist with file 1
   
}

}
[download]

Its not working, Since I want to print the output with respect to my file 1. If you can help with. I Know there is some error in 'If' statement. I could note understand that..

My version of the code works fine. It prints output for each line in file2 (like your original code). If you want output for each line in file1, then the code has to change since file1 and file2 have different formats.

#!/usr/bin/perl
use warnings; 
use strict;
use Data::Dumper;

my $file1 = <<END;
chr7    151046672
chr7    151047369
chr3    127680920
chr3    127680920
END

my $file2 = <<END;
chr1    66953622    66953654
chr1    67200451    67200472
chr1    67200475    67200478
chr1    67058869    67058880
chr1    67058881    67058885
chr7    151046672    127680920
chr7    151047369    127680920
chr3    127680920    151046672
chr3    127680920    151047369
END

open my $infile1, '<', \$file1 or die "unable to open first file $!";
open my $infile2, '<', \$file2 or die "unable to open 2nd file $!";

### create memory structure of file 1:
### so that we only have to read file1 once!
#

my %file1_hash;

while (my $line = <$infile1>)
{
   next if $line =~ /^\s*$/;   #skip blank lines (a common infile goof
+)
   
   my ($key, $value) = split /\s+/, $line; # use better "names" I have
                                           # no idea of what a chr col
+ means
   $file1_hash{"$key:$value"} = 1;
}
close $infile1;  # file handle closure is optional, but I'd do it.

###  process each line in file2:
###  If a line "matches" with any line in file1, then "E", else "M"
###  I don't know that these numbers mean, come up with better comment
+.

while (my $line = <$infile2>)
{
   chomp $line;  #so that output with E or M can be on same line
   next if $line =~ /^\s*$/;   #skip blank lines (a common infile goof
+)
   
   my ($chr, $val1, $val2) = split /\s+/,$line;
   
   if ( exists $file1_hash{"$chr:$val1"} or
        exists $file1_hash{"$chr:$val2"} )
   {
      print "$line\tE\n";  # match exists with file 1
   }
   else
   {
      print "$line\tM\n";  # match does NOT exist with file 1
   }
}


__END__
Prints the following:
chr1    66953622    66953654    M
chr1    67200451    67200472    M
chr1    67200475    67200478    M
chr1    67058869    67058880    M
chr1    67058881    67058885    M
chr7    151046672    127680920    E
chr7    151047369    127680920    E
chr3    127680920    151046672    E
chr3    127680920    151047369    E
[download]