use strict;
use warnings;

my $text="<tr><td>1</td><td>2</td><td>qw<font>3</font></td><td>4</td><tr>";

$text =~ s/<td>((?:(?!<td>).)*)3((?:(?!<\/td>).)*)/$1a$2/;
print "$text";

##</code><code>##

<tr><td>1</td><td>2</td>qw<font>a</font></td><td>4</td><tr>