The South American striker joined City in a £17million move from Blackburn in the summer but has been struggling to recover from a knee injury.
Hughes believes Santa Cruz will enjoy the same success at Eastlands as the likes of Craig Bellamy at Eastlands.
“Certainly there were a few eyebrows raised when I brought Craig to the club,” said Hughes.
“People doubted him and his ability. I certainly didn’t because I knew what I was getting.
“It will be the same with Roque. I know the talent he has. I know the attributes he has and I know what kind of guy he is.
“He is a driven guy. He is ambitious and he wants to win.
“The challenge is there, not just for him and Craig, but everybody in the squad.”