Inter can book their place in the Champions League Round of 16 as they host Barcelona, with Lautaro Martinez and Romelu Lukaku against Arturo Vidal and Antoine Griezmann.
It kicks off at a sold-out San Siro at 20.00 GMT.
The Nerazzurri will go through if they beat Barcelona, but that is not their only option.
If they finish level on points with Borussia Dortmund, then Inter have the upper hand due to a superior head-to-head goal difference record.
The Germans host Slavia Prague this evening.
Barcelona are already qualified and sure of top spot in the group, so can leave Lionel Messi, Sergi Roberto, Ousmane Dembele, Nelson Semedo, Jordi Alba, Gerard Pique and Arthur at home.
Luis Suarez is on the bench, as Griezmann and Carles Perez lead the attack.
There is playing time for Arturo Vidal and Ivan Rakitic, who have been repeatedly linked with moves to Inter and Milan.
As for Antonio Conte’s men, they are without Stefano Sensi, Nicolò Barella, Roberto Gagliardini, Kwadwo Asamoah and Alexis Sanchez.
Borja Valero therefore again steps in to the midfield, with Danilo D’Ambrosio and Cristiano Biraghi getting the nod on the wings ahead of Antonio Candreva and Valentino Lazaro.
As always, Lukaku and Lautaro Martinez lead the way, the Argentine finding the net in four consecutive Champions League games.
He had opened the scoring at Camp Nou before Inter capitulated 2-1 and has been repeatedly linked with a move to the Blaugrana for next season with his €110m release clause.
Both teams will wear special armbands representing Inter’s Buu campaign – Brothers Universally United – to combat racism.
Inter: Handanovic; Godin, De Vrij, Skriniar; D'Ambrosio, Vecino, Borja Valero, Brozovic, Biraghi; Lukaku, Lautaro Martinez
Inter bench: Padelli, Ranocchia, Candreva, Bastoni, Lazaro, Politano, Esposito
Barcelona: Neto; Wague, Lenglet, Umtiti, Junior Firpo; Rakitic, Todibo, Vidal; Alena, Griezmann, Carles Perez
Barcelona bench: Ter Stegen, Busquets, Suarez, De Jong, Fati, Araujo, Dani Morer
Ref: Kuipers (NED)
Watch Serie A live in the UK on Premier Sports for just £9.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit: https://www.premiersports.com/subscribenow