This is the competition Barca crave most of all, and the one that has delivered heartbreak over the last two seasons.
Barcelona head into the match in good shape after a 5-0 win over Eibar, while Napoli came from a goal down to beat Brescia on Friday night.
Let’s see who might play for Quique Setien’s side on Tuesday:
Barcelona are without Sergi Roberto and Jordi Alba due to injury which means Nelson Semedo and Junior Firpo are set to be the starting full-backs.
Setien needs to choose between Clement Lenglet and Samuel Umtiti at centre-back to partner Gerard Pique, while Marc-Andre ter Stegen will start in goal.
Frenkie de Jong should come back into the starting XI in Naples after getting a rest at the weekend, while Sergio Busquets should continue and is enjoying life under Setien.
Arthur was on target against Eibar and could complete the midfield, although Ivan Rakitic and Arturo Vidal are also in contention for a starting spot.
Martin Braithwaite will travel with the squad to Napoli but is not eligible to play, which means it’s down to Antoine Griezmann, Lionel Messi and Ansu Fati to supply the goals.
Setien has avoided playing all three in recent weeks but may be tempted to unleash the trio, as he will want an away goal to take back to the Camp Nou.
Possible XI: Ter Stegen; Semedo, Pique, Umtiti, Junior; De Jong, Busquets, Arthur; Messi, Griezmann, Ansu.
How do you think Barcelona will line up against Napoli? Let us know your thoughts, predictions and teams in the comments below!