The Andalusian neighbours will meet for the first time in European competiton when they face one another on Thursday
Real Betis can continue to confound their poor league form with Europa League success when they meet city rivals Sevilla on Thursday.
The 108th meeting between the two sides in all competitions will be the first time that the teams have met in a Uefa competition, adding extra spice to this season's round of 16.
Betis have belied their position at the foot of La Liga with their European exploits this term, losing just once in 10 games in the competition in 2013-14.
A 2-0 away win against Rubin Kazan saw Betis progress 3-1 on aggregate into the last 16, while Sevilla, who are unbeaten in their Europa League campaign, overcame Maribor 4-3.
The Estadio Ramon Sanchez Pizjuan will host the first leg and hosts Sevilla have romped to 4-0 and 5-1 wins in their last two home outings against Betis.
After a run of only one league win since the end September heading into last weekend, the Verdiblancos looked in danger of surrendering their top-flight status without a fight, but a 2-0 victory over Getafe on Saturday has restored confidence, setting up an intriguing tie on Thursday.