Both sides can still win the group and go directly through to the last 16, but the two are also in danger of elimination, with Sparta Prague waiting to pounce.
Match preview
In the only group where no side has yet sealed their place in the knockouts, everything is still to play for, but at least one of these sides will seal their spot in the Europa League in February here.
Betis lead the way, but they can still finish third, as they are just a point ahead of Rangers, and two ahead of Sparta.
Their current advantage means Manuel Pellegrini's side only need a point to progress, and having now gone unbeaten in 14 European home games - winning nine - that looks a distinct possibility.
A draw will also see Betis win the group as long as Sparta do not beat Aris Limassol by three or more goals, as it will go down to goal difference with the sides level on head-to-head.
However, a defeat for the hosts will likely see them eliminated, unless Sparta fail to win in Cyprus, meaning they would then edge through in second, so they must ensure there are no more slip-ups on the continent here.
Pellegrini has oversaw just two defeats in 18 matches, but they both came in Europe, going down away at Rangers and Sparta.
Betis kept their fine unbeaten domestic run going by drawing 1-1 with Real Madrid at the weekend, and while they are a long way off the top four, they remain in the hunt for the minor European places again.
Superb domestic form should also give Rangers serious hope in this trip to Southern Spain, as they are 13 games unbeaten.
That run started in Steven Davis's final game in caretaker charge, and new boss Philippe Clement has made an immediate impact since replacing Michael Beale.
As well as taking their hopes of progression in Europe down to the final matchday, Clement has also led Rangers to a cup final, and they have closed the gap on Celtic to five points, with a game still in hand.
However, the only notably poor result since the Belgian's arrival was a 1-1 draw with Aris on matchday five, as a win would have sealed their place in the knockouts.
Their superior head-to-head record over Sparta could still be important with just one point separating the sides, and both playing away this week, but Rangers will believe they may need a result here to go through.
That could be tough considering they have not won on any of their last 12 trips to Spain though, and it was in this city where they lost in the final of this competition just 18 months ago.
Real Betis Europa League form:
L
W
W
W
L
Real Betis form (all competitions):
D
W
L
D
W
D
Rangers Europa League form:
W
L
D
W
D
Rangers form (all competitions):
W
D
D
W
W
W
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Team News
Injuries have decimated the Betis midfield ahead of this clash, with Nabil Fekir and William Carvalho both out, and key man Guido Rodriguez struggling with an ankle injury.
Rodriguez was already an absentee with suspension though after picking up his third booking of the group stage last time out, but Hector Bellerin will be available after serving a domestic ban.
Defensive issues are mounting too though, with both Marc Bartra and Youssouf Sabaly on the sidelines currently, and players unavailable due to registration restrictions.
Sergi Altimira and Chadi Riad both started the last two games, and Sokratis Papastathopoulos is the next choice to come in at the back, but none are in Betis's Europa League squad, so will not feature here, with Altimira's absence likely to mean Marc Roca will be needed in midfield and therefore unable to fill in at centre-back.
Rangers have a substantial number of absentees themselves ahead of this clash, with midfield trio Tom Lawrence, Ryan Jack and Nicolas Raskin all missing.
Striker Danilo is also out injured, so Cyriel Dessers is set to start up front again after scoring in the win over Dundee at the weekend.
Jose Cifuentes was sent off in that weekend win, but his suspension will only be served in their next domestic outing, so he should start here.
Ross McCausland was superb in the second half of their draw with Aris, scoring the equaliser while causing headaches for the Cypriot defence after coming off the bench.
The youngster started the following two games, and played 45 minutes at the weekend, so he could well come back into the side here.
Real Betis possible starting lineup:
Rui Silva; Aitor Ruibal, Pezzella, Juan Miranda, Abner; Marc Roca, Guardado, Isco; Diao, Borja Iglesias, Ezzalzouli
Rangers possible starting lineup:
Butland; Tavernier, Souttar, Balogun, Barisic; Lundstram, Cifuentes, Cantwell; McCausland, Desserts, Sima
We say: Real Betis 1-0 Rangers
Despite major injury concerns ripping apart much of the Betis squad, their home form has been superb in Europe, and they should get the result they need to win the group.