Try the following:
string input = "my string will be 220,220,220,220";
string find = "220";
int searchIndex = input.IndexOf(find);
input = (searchIndex < 0) ? input : input.Remove(searchIndex, find.Length);
I've just noticed you tagged your question with
VB.NET
so here is the version for that language:
Dim input = "my string will be 220,220,220,220"
Dim find = "220"
Dim searchIndex = input.IndexOf(find)
input = If((searchIndex < 0), input, input.Remove(searchIndex, find.Length))