The retired Spain star feels his ex-club still have a chance of reaching Wembley, but admits they will have to work harder than ever before to achieve that goal
Los Blancos were defeated 4-1 by Jurgen Klopp's side at Signa Iduna Park last week, and they will now look to turn the tie around and proceed to the finals of the competition.
And Santillana conceded that although Jose Mourinho's team is blessed with a number of quality players, that is ultimately not enough to prevail in modern football.
"You don't just win football matches with quality, which is what we have, you also have to be clever at certain points of the game," the 60-year-old told Marca.
"You must fight to the death for every ball."
The retired Spain star then reflected on famous comebacks he was involved in during his playing career.
He said: "When we managed to turn around games that we were losing, we were all convinced after in the changing room that we could come back from anything at the [Santiago] Bernabeu.
"Apart from being focused, you had to put the opponent under real pressure, fight for every ball as if it were the last thing you did in life."