The 22-year-old was hauled off in the 47th minute of City’s 3-2 defeat by Manchester United on Sunday after an ineffective display at The Etihad.
It prompted a fresh wave of speculation about Balotelli’s future at the Premier League champions, with the Italy international only scoring once in 13 league appearances this season.
“Balotelli is not for sale,” Mancini told Sky Sport Italia.
“Mario is a City player, he is loved by the fans and the management. He has been an important player for us.
“A player of his quality should think exclusively to his work and his family, he has talent and he cannot blow it as he is doing.
“Our paths may separate if I change team, but he will remain at City.”
Meanwhile, the Citizens manager also insisted he was happy at the Eastlands outfit despite a premature exit from the Champions League and falling six points behind United in the Premier League title race.
“I’m fine at City,” said Mancini. “I work in a very serious club and in England it is easier to work. There is a project and we have done a great job in two years.
“I feel really good, but it is clear that I miss Italy because home is always missing.”