Fiorentina need victory in Hungary to qualify for the Conference League after their thrilling 3-3 first leg draw with Puskas Akademia, as Moise Kean and David De Gea start.
The play-off kicks off at the Pancho Arena in Felcsut at 20.00 UK time (19.00 GMT).
The first leg was a chaotic 3-3 draw, which saw the Viola trail 2-0 in the opening minutes, fight back to lead 3-2 only to concede late on.
All three competitive matches for new coach Raffaele Palladino have been disappointing draws with Parma, Puskas Akademia and Venezia.
Because away goals do not count double, it effectively means that winner takes all tonight, or it goes to extra time and penalties.
There are several changes from the first leg, with Dodo and Cristiano Biraghi stepping in, plus Amir Richardson in midfield and Kean upfront.
De Gea is in goal, whereas it was Pietro Terracciano for the two Serie A matches.
New signing Albert Gudmundsson is still out injured and Yacine Adli arrived too late to be registered.
Puskas Akademia vs. Fiorentina line-ups
Puskas Akademia: Pecsi; Maceiras, Golla, Stronati, Zs. Nagy; Plsek, Favorov, Nissila; Soisalo, Pujic, Levi
Fiorentina: De Gea; Martinez Quarta, Pongracic, Ranieri; Dodò, Amrabat, Richardson, Biraghi; Ikone, Sottil; Kean
Ref: Nobre (POR)