If you mean an "in use" drive with programs and data on it - then it's possible but fraught with danger.
Before you even consider it, you need to back up the entire contents of the drive. And then defragment it.
Can you explain a bit further the whys and wherefores of what you want to do - then some more practical advice may be given. There's usually no vital need to partition an "in-use" drive.
Free bootable Linux which has GPartEd (which I've used to partition NTFS Windows drives) can be found from here click here