Yes it will. The Real Tone Cable is compatible and required for all versions of Rocksmith.
How do you connect a guitar to Rocksmith?
All you need to do is plug in your guitar into your interface, connect it to your computer via USB and fire up Rocksmith. The intended purpose of this mode is to allow you to connect an acoustic guitar to Rocksmith, but it'll recognize your audio interface as well. Select your audio interface and you're done.