Juan Antonio Pizzi's side pulled off a stunning turnaround in the previous round against Basel and, trailing 2-0 this time, they will be hoping for similar fireworks
Juan Antonio Pizzi's men looked to be crashing out after the first leg of their quarter-final tie with Basel following a 3-0 defeat in Switzerland but mounted an incredible comeback at Mestalla.
Paco Alcacer scored a hat-trick as the Spanish side secured a stunning 5-0 win after extra time as Basel crumbled but Valencia have again left themselves with a lot to do in the return leg against their countrymen.
Quick-fire goals from Stephane M'Bia and Carlos Bacca in the first half earned Sevilla a 2-0 advantage in the first game, with ex-Valencia boss Unai Emery getting one over on his ex-employers.
Both sides have enjoyed success in this competition in recent years. Valencia lifted the trophy in 2004 under Rafael Benitez, while Sevilla are the only side to have defended their title since the tournament switched to a one-off final in 1998 - with wins in 2005 and 2006 against Middlesbrough and Espanyol, respectively.
The prize for progressing to another final will be a clash with Italian giants Juventus or Portuguese champions Benfica in Turin on May 14.
The hosts go into the game on the back of a 1-0 defeat to title-chasing Atletico Madrid, a result which leaves them eighth in the Primera Division table and unable to qualify for next year's competition through their league placing.
Valencia have had the better of the two league meetings this season, winning 3-1 at Mestalla and then securing a goalless draw in Sevilla - and they will need to make the most of home advantage again on Thursday.
Sevilla are enjoying a strong season under Emery, having won 13 of their last 17 games in all competitions. They were beaten 3-1 at Athletic Bilbao last time out, though, in a game which put a huge dent in their Champions League qualification hopes.
Emery's men are now six points behind Athletic in the race for fourth place, with only three matches remaining and an inferior head-to-head record with the Basque outfit.
Sevilla also had to come from behind in their quarter-final, losing the first leg 1-0 in Porto before hammering Luis Castro's men 4-1 in the return game at the Estadio Ramon Sanchez Pizjuan.
They will be hopeful that Bacca - who has seven goals in this year's tournament and 21 in all competitions - can net them a crucial away goal that could put the tie beyond their hosts but will be wary of the threat of Alcacer, whose treble in the comeback win over Basel moved him level with Bacca on seven goals in the competition.
Valencia duo Diego Alves and Philippe Senderos (both hamstring) are doubts, while Victor Ruiz (thigh) is definitely out. The visitors are without Sebastian Cristoforo (knee) and Denis Cheryshev (foot), while defender Daniel Carrico is a doubt with an ankle problem.