Published: 2016-08-25 12:57:26 BdST
But this time, he's not the one throwing the punches, he's training famed Panamanian fighter Roberto Duran, portrayed by Edgar Ramirez.
Following a world premiere at the Cannes Film Festival in May, the film celebrated its upcoming release on the red carpet at a New York premiere on Monday evening.
De Niro, 73, who won an Oscar for the boxing movie "Raging Bull" in 1981, plays Duran's trainer Ray Arcel.
Singer Usher takes on Duran's rival as Sugar Ray Leonard and also provided the film's theme track.
"For every great movie there is a song. For every great moment there's a song," said Usher. "Music is the greatest communicator of emotion and time."
Although the film is centred on the life and career of Duran, 65, the film's star said the sport is just the context.
"It could have been golf, it doesn't matter," said Ramirez. "It's a human story, a universal story,"
Cuban actress Ana de Armas, who has the role of Duran's wife, spoke to Ramirez's point, opining that the film is rooted in love.
"This movie isn't only about boxing, it's a beautiful love story. When people see, they'll understand how important Felicidad is in Duran's life," she said.
"Hands of Stone" will be released in the US theatres on Aug 26.