The German club were unbeaten in the two matches against Madrid in the group stage, beating Jose Mourinho's side 2-1 and recording a 2-2 draw in the Spanish capital.
Hummels believes that his team must keep the ball well if they are to reach the final at Wembley.
"Ball possession will be a key factor against Real Madrid," the defender told FIFA.com.
"I remember our match at the Santiago Bernabeu during the group stage. In the second half we did not have the ball for longer than 10 seconds before we lost it again, and then it is really difficult against them."
The first leg of the tie takes place on Wednesday evening.