With their fragile away form in Europe and scars from last season's capitulation away at Liverpool, Barcelona are contending with a lot of pressure.
Much of that is self-inflicted due to the alleged manipulation of social media coverage of the team from club president Josep Maria Bartomeu - who recieved boos from the home fans at the Nou Camp at the weekend.
Messi is of course constantly compared to Diego Maradona, with tonight's game at the former home of the former World Cup winner.
Here are the predicted line-ups for what promises to be a compelling knock-out tie.
What time is Napoli vs Barcelona?
The match kicks off at 8pm GMT (9pm local time) at the Stadio San Paolo in Naples.
How can I watch on TV?
Yes, you can watch the game live on BT Sport 3 with coverage beginning at 7:15pm.
Can I stream it online?
Yes, BT Sport subscribers will be able to stream the match online via the video player and the BT Sport app.
Napoli: Ospina, Di Lorenzo, Manolas, Maksimovic, Rui, Fabian, Demme, Zielinski, Callejon, Mertens, Insigne. Subs: Meret, Allan, Elmas, Luperto, Politano, Hysaj, Milik.
Barcelona: ter Stegen, Nelson Semedo, Pique, Umtiti, Firpo, Busquets, Rakitic, de Jong, Vidal, Messi, Griezmann. Subs: Arthur, Neto, Lenglet, Puig, Fati, Araujo, Akieme.
Lionel Messi is almost destined to score at the house that Diego Maradona helped build, but their lack of stability off the pitch may creap into their game on it when Napoli pick up momentum. Not to mention their track record of collapsing somewhat in away knockout ties. Gennaro Gattuso will inject the right amount of motivation into his side on this big night in Naples and could well pinch a slender 2-1 lead heading into the second leg.