The Portuguese defender is back after serving a one-game suspension in an otherwise unchanged side for Jose Mourinho's men with Sami Khedira keeping his place in midfieldJose Mourinho has made only one change from the side who thrashed Espanyol 5-0 last weekend with Pepe coming into the centre of defence after serving a one-game suspension.
The former Porto defender comes in for his compatriot, Ricardo Carvalho, who is serving a one-match ban after picking up his fifth yellow card of the season against Mauricio Pochettino's men.
With Madrid otherwise unchanged, the likes of Esteban Granero, Jose Callejon and Karim Benzema have to make do with places on the bench with Sami Khedira, Kaka and Gonzalo Higuain keeping their places in the starting XI.
Pepe Mel has decided to stick with the same side who suffered a 3-1 defeat to Levante on Monday night with the likes of Roque Santa Cruz and Juanma listed as substitutes.
Real Betis (4-3-3): Fabrizio; Nelson, Paulao, Dorado, Nacho; Salva, Iriney, Benat; Castro, Molina, Montero.
Real Madrid (4-2-3-1): Casillas; Arbeloa, Pepe, Ramos, Marcelo; Xabi Alonso, Khedira; Ronaldo, Kaka, Ozil; Higuain.