With Barcelona 13 points clear at the top, Madrid boss Jose Mourinho will know that a runners-up spot is as good as they can earn, and victory over Betis will put the pressure on Atletico Madrid.
Mourinho could name the same team that recorded a 3-0 win over Athletic Bilbao last weekend.
Betis stunned Sevilla last weekend, fighting back from 3-1 behind to earn a 3-3 draw to keep them in contention to secure a European place next season.
Manager Pepe Mel would have taken great confidence from his side's comeback against Sevilla, and that could lead to him beginning the match at the Bernabeu with the same team.
Real Madrid: DWWLW
Real Betis: WLDWD
Possible starting lineups
Real Madrid: Diego Lopez; Sergio Ramos, Albiol, Pepe, Marcelo; Xabi Alonso, Modric, Khedira; Di Maria, Cristiano Ronaldo, Benzema
Real Betis: Adrian; Javi Chica, Paulao, Antonio Amaya, Alex Martinez; Benat, Canas, Juan Carlos, Ruben Castro; Pabon, Campbell
Sports Mole says: 4-1