The Oscar-winning star has teamed up with BD Hotels and property firm Capco to open The Wellington Hotel near the Royal Opera House.
It will act as a sister site to De Niro’s Greenwich Hotel in New York which he opened in 2008 with his son Raphael and hoteliers Ira Drukier and Richard Born.
The London venue will include two restaurants, a spa, a deli/café, and a member’s club built around a central courtyard area.
If the plans are approved by Westminster City Council, work would begin in 2017 and the hotel would open in 2019.
De Niro said in a statement: “London is one of the most exciting and cosmopolitan cities in the world. It makes perfect sense to develop a hotel that represents all of that in the heart of this city in Covent Garden.
“The Wellington Hotel would honour the heritage of the area, while bringing the best of what we’ve done in New York to London.”
De Niro is set to act as joint operator of the hotel.