The 49-year-old was removed from his position at the San Siro in 2008 but the former Manchester City boss has returned to replace outgoing manager Walter Mazzarri.
Mancini won three Serie A titles during his previous reign but he has been given the task of trying to get the club back in the top three to earn Champions League football next season.
Rivals AC Milan are one point and two places better off than Inter in the standings, but Filippo Inzaghi has seen his side fail to win in the league for four matches.
Three draws have come during that period, but their last victory came back on October 19 against Hellas Verona.
Striker Fernando Torres could be recalled to the starting lineup but the Spaniard is under pressure to improve on a scoring record that has seen him net just once in nine games.
Midfielder Nigel de Jong is an injury doubt with a hamstring problem that saw him sidelined during the international break, while Daniele Bonera is suspended after two yellow cards saw him get sent off at Sampdoria.
Recent form: WWDDLD
Possible starting lineup: Diego Lopez, Zapata, Mexes, Rami, De Sciglio, Essien, Menez, De Jong, Bonaventura, Honda, El Shaarawy
Form in Serie A: LDWWLD
Form in all competitions: DWWLDD
Possible starting lineup: Handanovic, Vidic, Nagatomo, Ranocchia, Dodo, Juan, Kuzmanovic, Obi, Kovacic, Palacio, Icardi
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