Record champs Sevilla – who won the competition in 2006, 2007, 2014 and 2015 – needed a penalty shoot-out against Athletic Bilbao in the quarter-finals and now meets 2009 winners Shakhtar Donetsk in the semis.
Should they progress to the May 18 final in Basel, Switzerland, they could find compatriots Villarreal waiting if they can overcome Juergen Klopp’s Liverpool in the other tie.
The current holders Sevilla will be without veteran Jose Antonio Reyes for Thursday’s first leg at Shakhtar, due to an emergency operation for appendicitis.
Reyes is also likely to miss the May 5 second leg in Seville.
But coach Unai Emery will be able to count on fit-again players Vitolo, Benoit Tremoulinas and Nico Pareja. Emery’s team confirmed their good form
“We are very close to reaching another final,” Sevilla president Jose Castro said.
“This is an important moment for our club. We will be fighting hard to reach the final.”
The two teams have history dating back to a spectacular round of 16 tie in 2007 which Shaktar were winning until the Sevilla goalkeeper equalized four minutes into injury time in the second leg. Sevilla won in extra-time and went on to lift the trophy.
“It was a painful defeat,” Taras Stepanenko UEFA.com. “(Coach Mircea) Lucescu told us about it in training, and some of the older players remember it.
“It was hard for them to concede a goal from Sevilla’s goalkeeper in the last minute – things like that don’t normally happen. We would like some revenge for that.”
The first leg will be played in Lviv, some 1,000 kilometres from Donetsk, due to the political situation in Ukraine.
“We’re playing away all the time, and now that we’re playing every three days we almost never see our families, but we keep working and our successes prove it’s not in vain,” Stepanenko said.
Meanwhile, Villarreal begin their bid to reach their first ever final in any competition, at home to seasoned campaigners Liverpool.
The Yellows’ only injury doubt is veteran striker Roberto Soldado.
“We want to be in the final, that would be really beautiful for this club. We are just two games away now, though we are facing historic rivals,” said Villarreal playmaker Denis Suarez, who helped Sevilla to win the competition in the last two years on loan from Barcelona.
Villarreal also have history on their minds dating back to their last European semi-final in 2006, when a late missed penalty cost them a place in the Champions League showpiece.
“That was a cruel moment for this club,” Suarez said. “Everyone here has bad memories of that. Now we have the chance to try to make amends for that.”
Coach Klopp has a selection dilemma to contemplate en route to Spain as Liverpool seek to match Sevilla’s record of four tournaments wins.
With Mamadou Sakho suspended internally as he is investigated for a failed drugs test, Klopp must decide who should partner Dejan Lovren at the heart of defence.
“We have Martin (Skrtel), Kolo (Toure), Lucas and Tiago Ilori so we have a few players who can play centre-half,” he said.
Toure said he would be delighted to help his side, if picked.
“If they call me up, of course I will be really happy,” he said.
“For me, the most important thing is the club, the team. It is going to be a big two games and you need to do your best for the club.
Jordan Henderson, Emre Can and Divock Origi are also out through injury but Nathaniel Clyne is expected to return after missing the weekend draw with Newcastle because of illness.