As a follow-on to Pramod's answer for users who have checked the box at Configure > Preferences > General > Allow multiple instances to run
you'll need to make sure that the instance of Textpad that has your changes is the last one to be closed, or copies with the previous set of settings will overwrite your new settings when they close.
To get your preference changes to stick around, close all but one instance of Textpad, change the settings, and then close that last copy of Textpad.
This goes for any Textpad preference, including showing line numbers.
Why:
Each instance of Textpad saves its settings when it closes (not when you change the setting, which is what you would think would happen).
Every time an instance of Textpad closes, it rewrites the full set of settings, even if you didn't change them in that instance (behavior which I would classify as a bug).
This means that if you have two instances of Textpad open (call them 'A' and 'B') and you change some preferences in instance 'A', but then you close instance 'A' and then you close instance 'B', the set of preferences from instance 'B' wipe out the settings you just changed in instance 'A' and you don't get them back.
To save your preferences effectively, you need to make sure that the last open instance of Textpad is the one that has your changes, and then you need to close that instance.
After that, any instance you open will have the new settings.
This bothered me for a while before I figured it out.