The top two teams in Europa League Group F meet again in southern Spain two weeks after Betis pulled off a surprise 2-1 win over AC Milan at the Stadio San Siro, to leapfrog the Italian side to the top of the section.
Betis will be through should they win and Olympiacos fail to do so at home to Dudelange, who have lost their first three matches.
The Rossoneri have a wealth of experience against Spanish opposition, playing 56 matches in total but winning just 18 of them and only four of 25 in Spain, with each of their last five matches there ending in defeat.
Real Betis: Pau Lopez; Mandi, Bartra, Feddal; Tello, Lo Celso, W. Carvalho, Canales, J. Firpo; Joaquin, Sanabria.
AC Milan: Reina; Musacchio, Zapata, Rodriguez; Borini, Kessié, Bakayoko, Calhanoglu, Laxalt; Suso, Cutrone