Ronald Koeman's side booked their spot in the semi-finals of the Copa del Rey with a 5-3 victory over Granada on Wednesday, but Betis lost on penalties to Athletic Bilbao to exit the competition.
Betis saw their Copa del Rey challenge come to an end on Thursday evening as they lost on penalties to Athletic, who had levelled the scores at 1-1 in the final exchanges through Raul Garcia.
Manuel Pellegrini's side will now switch their attention back to La Liga, where they are currently on a five-game unbeaten run, recording three wins during that spell against Huesca, Celta Vigo and Osasuna.
Betis have had their problems this season - suffering nine defeats from 21 La Liga matches - but a total of 30 points has left them in seventh spot in the table, just two points behind sixth-placed Real Sociedad.
The Green and Whites finished a disappointing 15th in Spain's top flight last term but are currently challenging for a potential Europa League spot, which would represent an excellent campaign.
A run of three wins from their last four La Liga matches means that Pellegrini's side will enter this match full of confidence, but they have lost each of their last four games with Barca.
As mentioned, Koeman's team advanced to the semi-finals of the Copa del Rey on Wednesday courtesy of a 5-3 win over Granada; the Catalan giants actually trailed 2-0 entering the final exchanges but managed to score twice to force extra time before triumphing in impressive fashion.
Barca will face Sevilla in the semi-finals of the cup next week, while there is also a Champions League clash with Paris Saint-Germain on the horizon, with the two teams locking horns in Spain for the first leg of their last-16 tie on February 16.
The Catalan side cannot afford to shift their focus away from the league, though, as the gap to leaders Atletico Madrid is currently 10 points, with Diego Simeone's side also having a game in hand.
Second-placed Barca need a miracle to rise to the summit, but they are above champions Real Madrid in the table and have won each of their last five in the league, including a 2-1 success over Athletic last weekend.
The 26-time Spanish champions are actually unbeaten in Spain's top flight since the start of December, and it could still be a successful campaign for the club despite their troubles.
Real Betis La Liga form: LDWWDW
Real Betis form (all competitions): WWDWWL
Barcelona La Liga form: DWWWWW
Barcelona form (all competitions): LWWWWW
Diego Lainez, meanwhile, is still unavailable, having recently tested positive for coronavirus.
Pellegrini will definitely make changes from the side that started against Athletic in the Copa del Rey, with Joaquin, Emerson, Rodri and Loren Moron all in line to feature, but Guido Rodriguez should keep his spot in midfield, lining up alongside Sergio Canales in the process.
Sergio Busquets was suspended against Athletic last weekend but should return to the XI here, having been involved against Granada in the Copa del Rey, while Ousmane Dembele and Antoine Griezmann are again expected to feature alongside Lionel Messi in attack.
Real Betis possible starting lineup:
Joel; Emerson, Mandi, Ruiz, Moreno; Rodriguez, Canales; Joaquin, Rodri, Fekir; Moron
Barcelona possible starting lineup:
Ter Stegen; Dest, Araujo, Lenglet, Alba; Pedri, Busquets, De Jong; Dembele, Messi, Griezmann
We say: Real Betis 1-2 Barcelona
Betis certainly have the talent to cause Barca problems, and it should be an open and entertaining clash in Seville; we are expecting the home side to score but are finding it difficult to look past Koeman's side, who must keep winning and hope that Atletico drop a number of points in the coming weeks.