The actor, director and producer will lead the panel for the third time at the 64th annual festival, which takes place from May 11 to 22.
De Niro said: "The Cannes Film Festival is a rare opportunity for me as it is one of the oldest and one of the best in the world.
"As co-founder of the Tribeca Film Festival and the Doha Tribeca Film Festival, I have an increased appreciation for the jury who serve, undertaking an important role in choosing films that are represented in the world of film at its highest level. These types of festivals help connect the international film community and have a lasting cultural impact.
"Having served as president of the jury in the '80s twice, I know this isn't an easy task for me or my fellow jury members, but I'm very honoured and happy to head the jury for this year's Cannes Film Festival."
Two films starring De Niro - 1976's Taxi Driver and 1986's The Mission - have won the Palme d'Or at Cannes.
Last year's jury was headed by director Tim Burton. The Palme d'Or was won by Uncle Boonmee Who Can Recall His Past Lives.