Speaking on the trade and financial embargo in place since 1962, Hollande said France will do whatever possible to see that "the measures that have so badly harmed Cuba's development can finally be lifted, repealed."
Hollande, the first French president ever to visit Cuba, said his trip came "at a particularly important but also uncertain time," as both the United States and the European Union seek to restore diplomatic relations with Havana.
France will do what it can to "see that opening reaffirmed," he said in an address at the University of Havana.
Since announcing in December that the United States and Cuba would move to renew ties after more than half a century, President Barack Obama has used his executive authority to relax several aspects of the US embargo, including restrictions on travel and sending money to the island.
He has called on Congress to lift the full embargo, but with both houses under Republican control, he faces an uphill political battle.
The French president is due to meet with his Cuban counterpart Raul Castro on Monday and his office has said he is available to meet with revolutionary icon Fidel Castro as well.
However, Havana has not confirmed that a meeting between Hollande and Fidel Castro will take place.
The visit follows a meeting Sunday between Raul Castro and Pope Francis at the Vatican, where the Cuban leader thanked the pontiff for his role in brokering the historic détente between Havana and Washington.