Let me guess. Powered speakers with three prong power cords? The problem is that your computer's digital ground is crap. All the digital noise passes through the shield of the USB cable, down the shield on your audio cables, and into the speakers because the speakers have a much better ground. However, when the noise passes through the audio cable shields, some of that noise bleeds into the audio.
There are two ways to cure this:
1. Ground your audio interface better.
2. Use balanced audio cables between the interface and speakers with the grounds lifted on one end.
I suggest #1; with some microphones, you might get noise on your inputs as well, and #2 won't solve that problem, but #1 should. That said, you could do #2 and attempt #1 later if you run into that problem.