The Red Devils have only dropped two points in their last 25 home matches, and the Portugal international believes that their North West opponents will endure a tough contest.
"City have a fantastic team at the moment with fantastic players," said Nani. "They are playing a lot of good stuff and it will be difficult to play against them.
"But we should not forget; we are United. When we play at home it is very hard to beat us. That is why we are so confident.
"With a record like ours, we should be confident every time we play at home. We have to believe we are going to win most of the games."
The Premier League showdown is scheduled for Sunday afternoon.