A substitution will always default to whatever the current value of $_ is. I think your real question is "If I use something as the operand of a match operator, does that set $_ to it?" The answer to that is no.

What it looks like you're trying to do is take an lvalue to the result of $table->cell($rownum, 0..2). This is, generally, not something that's recommended to be done (though it is doable, kinda). Much better would be to have the $table object be asked to normalize the value that would be returned by $table->cell($rownum, 0..2) within the object itself. That way, you're probably using some sort of hash value. Even then, you can't do the whole $_ lvalue thing. Honestly, I don't like code that overuses $_. Just be explicit about what you're doing.

Now, instead of trying to reuse the operand, you could make the match and substitution a little smarter.

my $strip = '\x0';
$strip .= '\d+' if $table->cell($rownum, 0..2) =~ $strip;
$table->strip( $strip, $rownum, 0..2 );
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That requires coding up another method that would do something like

# The ... indicates "Whatever" - it's not meant to be syntatically-cor
+rect Perl.
sub strip {
    my $self = shift;
    my ($pattern, ... ) = @_;

    $self->{cells}[...] =~ s/$pattern//;
}
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See how that could work better?