The France striker is back from injury but has to settle for a place amongst the substitutes as the Portuguese defender returns after serving a one-game suspension
The former Porto defender slots into the rearguard to replace his compatriot Ricardo Carvalho, who is serving his own one-match ban after picking up a fifth yellow card of the season against Mauricio Pochettino's men.
Karim Benzema has made a full recovery from his muscle strain but will only start from the bench as Gonzalo Higuain retains his place up front.
With Los Blancos otherwise unchanged, the likes of Esteban Granero, Jose Callejon and Lass Diarra have to make do with places on the bench with Sami Khedira and Kaka keeping their places in the starting XI.
Pepe Mel has decided to stick with the same side that slumped to a 3-1 defeat to Levante on Monday night, with Roque Santa Cruz and Juanma listed only as substitutes.
Real Betis (4-3-3): Fabrizio; Nelson, Paulao, Dorado, Nacho; Salva, Iriney, Benat; Castro, Molina, Montero
Subs: Casto, Matilla, Canas, Pozuelo, Juanma, Santa Cruz, Super
Real Madrid (4-2-3-1): Casillas; Arbeloa, Pepe, Ramos, Marcelo; Xabi Alonso, Khedira; Ronaldo, Kaka, Ozil; Higuain
Subs: Adan, Granero, Benzema, Albiol, Varane, Callejon, Diarra