The 49-year-old managed Sevilla during the 2011-12 campaign, though he failed to see out the season before returning to football with Villarreal in 2013.
Marcelino acknowledged that his sacking hurt, but with the two Spanish sides - separated by just a point in La Liga - set to clash in the Europa League last 16, he has the chance to prove a point to those who doubted him at the Ramon Sanchez Pizjuan.
"I am very grateful to the Sevilla for giving me the opportunity to coach this great club," he said.
"Sometimes things don't go as you'd like, as with everything in life. You can suffer, but you always need to look forward.
"It hurt me at the time of the dismissal. Then, the immediate response was frustration.
"From then you analyse the situation and try to find out what went wrong and not to repeat it."
After finishing second in Group A, Villarreal cruised past Red Bull Salzburg 5-2 on aggregate in the last 32.
Marcelino's men go into the first leg on the back of a 4-1 triumph over Celta Vigo on Sunday, with Luciano Vietto among the scorers to take his tally to 19 for the season in all competitions.
But, in Sevilla, Villarreal face a team who are used to success in this competition, having beaten Benfica to lift the trophy last season.
Unai Emery's men produced a devastating counter-attacking display at Borussia Monchengladbach in the previous round, winning 3-2 in Germany to secure a 4-2 aggregate win against the Bundesliga high-flyers.
However, midfielder Vicente Iborra accepts that Sevilla must get better defensively if they are to continue their run in this season's Europa League.
"We have to improve, obviously, because we have conceded lot of goals away from home. It's a bleeding we must stop," he said.
The return of Daniel Carrico should help matters for Sevilla, as the Portuguese defender comes back from a groin strain, but Beto (shoulder) and Sebastian Cristoforo (knee) are definitely out.
Marcelino also has a few injury concerns to take into consideration, with Eric Bailly (hamstring), Bruno Soriano (fibula), Bojan Jokic (knee) and the suspended Tomas Pina not involved.
