Quique Setien’s men won a seven-goal thriller at the Camp Nou earlier this season and have had the week to prepare for the match, while Barca have been in Champions League action.
With that in mind, let’s have a look at who might feature.
Ernesto Valverde is likely to make a few changes in defence which could mean Samuel Umtiti taking Clement Lenglet’s place at centre-back.
The defender missed out on facing former team Lyon in midweek but needs games as he continues his lengthy comeback from knee trouble.
Nelson Semedo may also return to the starting XI at right-back in place of Sergi Roberto.
Elsewhere, goal-machine Gerard Pique has played every single La Liga minute so far but doesn’t look like getting a rest any time soon, while Jordi Alba and Marc-Andre ter Stegen should also feature.
Arturo Vidal could return to the starting XI in a bid to give the midfield some fresh legs against Real Betis.
The Chilean has been impressive in recent weeks, both starting and coming off the bench, and has clearly earned Valverde’s trust after a somewhat sticky start.
Carles Alena is another option in midfield, although it seems likely both Ivan Rakitic and Sergio Busquets will continue at what is a tough away ground.
Valverde has decisions to make in attack with Ousmane Dembele sidelined again with a hamstring injury.
Philippe Coutinho replaced him in the starting XI against Lyon and put in an improved showing. He could continue alongside Lionel Messi and Luis Suarez.
Malcom is another option to come into the attack and add some pace, although he may have to settle for a place on the bench.
Possible XI: Ter Stegen; Semedo, Pique, Umtiti, Alba; Rakitic, Busquets, Vidal; Messi, Suarez, Coutinho.
How do you think Barcelona should line up against Betis? Let us know your thoughts, predictions and line-ups in the comments below!