Fiorentina choose Giovanni Simeone and Federico Chiesa to lead their attack, while Inter rely on Lautaro Martinez and Radja Nainggolan.
It kicks off at the Stadio Franchi at 19.30 GMT.
This is becoming a huge game for the Nerazzurri, who have impressed in the absence of Mauro Icardi, the striker who hasn’t featured – officially due to a knee injury – since he was stripped of the captaincy last week.
Lautaro Martinez is the only available option as centre-forward, seeing as Keita Balde Diao is injured, with Matteo Politano, Radja Nainggolan and Ivan Perisic in support.
Marcelo Brozovic joins ex-Fiorentina star Matias Vecino in midfield, leaving Borja Valero on the bench, with Dalbert in for Kwadwo Asamoah.
The pressure is growing on Luciano Spalletti, because Inter are in third place on 46 points, followed by Milan on 45 and Roma 44.
Fiorentina are forced to do without Kevin Mirallas and German Pezzella, but Vincent Laurini returns to the starting XI.
The big change from Stefano Pioli is dropping Luis Muriel in favour of Simeone, with Gerson chosen to complete the trident attack with star man Chiesa.
The Viola are unbeaten in eight competitive games and have only failed to score once in their last 13 official meetings with Inter.
It is a reunion for Pioli, who was sacked by Inter in May 2017 after just 27 competitive games in charge. Pioli has never been able to beat former Roma Coach Spalletti, managing just two draws from nine meetings.
This fixture is famously entertaining, as there have been 31 goals in the last seven encounters between Fiorentina and Inter, including a 5-4 thriller in 2016-17.
Fiorentina: Lafont; Laurini, Ceccherini, Vitor Hugo, Biraghi; Benassi, Edmilson Fernandes, Veretout; Gerson, Simeone, Chiesa
Fiorentina bench: Terraciano, Brancolini, Milenkovic, Hancko, Graiciar, Norgaard, Dabo, Pjaca, Muriel
Inter: Handanovic; D'Ambrosio, De Vrij, Skriniar, Dalbert; Vecino, Brozovic; Politano, Nainggolan, Perisic; Lautaro Martinez
Inter bench: Padelli, Cedric, Miranda, Ranocchia, Asamoah, Joao Mario, Gagliardini, Borja Valero, Candreva
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