I have a screen in mainframe in which if the user changes something, it will give a popup “Do you want to confirm the changes and go to 21 screen(Y/N):_

Hi Kumar,

There can be several reason for this behavior.
Are you implementing any host logic when you start the update process, like executing a path procedure or submitting a GXSendKeyRequest?

You can try any workaround this issue by avoiding that popup screen altogether. When you update, instead of hitting ENTER the getting a popup window , typing y/n + ENTER again and only then perform the update.
You can use the JavaScript Confirm function (OK- CANCEL box) to execute a path procedure that will perform the whole update process, including the confirmation. If the user clicks CANCEL in the Confirm box , nothing will happen. See the following example

function confirmUpdate(){
if (confirm('Are you sure?'){
gx_postBack('doUpdate'); // Execute a server side update method
}
else{
// do nothing
}
}

This solution will shorten the the update process since the users don’t have to wait for the Host confirmation popup.

Hope this helps,
Ohad