Firmino gets the nod ahead of Daniel Sturridge, who again has to settle for a substitute role in Europe.
Joe Allen lines up alongside Lucas and James Milner in a three-man midfield.
There’s another change from the side that started against Newcastle on Saturday, with Nathaniel Clyne returning at right-back.
Christian Benteke is also on the bench.
Kick off at Estadio El Madrigal is 8.05pm BST.
Liverpool: Mignolet, Clyne, Toure, Lovren, Moreno, Lucas, Allen, Milner, Lallana, Coutinho, Firmino.
Subs: Ward, Benteke, Sturridge, Skrtel, Ibe, Smith, Chirivella.
Villarreal: Asensio, Mario, Bailly, Víctor Ruiz, Jaume Costa, Pina, Bruno, Dos Santos, Denis Suárez, Soldado, Bakambu.