Ronaldo is expected to travel to the Mestalla to support his teammates, but will play no part in the match due to a hamstring injury.
Santillana believes that the capital outfit can claim the trophy, but has admitted that the loss of Ronaldo is a blow to their chances.
"Real Madrid have played and won without Ronaldo before. They have coped with his absence as a team," Santillana told Goal.com.
"But there's no denying that he gives something extra to the team, just like Lionel Messi does to Barcelona.
"They have so much quality that they can win titles on their own and the rest of the team knows that. A team consists of 11 players, but fact remains that Ronaldo and Messi are the best in the world."
Santillana represented Madrid from 1971 until 1988.