Mourinho has been handed a stadium ban by the Football Association following his confrontation with referee John Moss in the 2-1 defeat against West Ham.
"I've been here almost two years now and we have not played without the coach yet, so it is going to be strange, but this is football and we will be ready," Matic said.
"Of course it is easier when the coach is on the bench, especially at half-time when he can say something.
"Sometimes when the game is stopped and there is a foul, he signals with the hands and you know what you have to do. But if you are playing on his side of the pitch you can hear him!
"We also have other great coaches here, and they will be prepared for everything. We have to be ready."