A historic warming of Cuba-US relations, dubbed the Cuban Thaw, began in December 2014 as the two countries look to reopen respective embassies in Havana and Washington for the first time in more than 50 years.
"I thanked His Holiness for his contribution to the restoration of relations between Cuba and the United States," Castro said after the audience as quoted by the Tgcom24 television channel.
Castro visited the Vatican after attending the Victory Day Parade in Moscow and was given an hour-long private audience by the pontiff.
Pope Francis is set to become the third head of the Catholic Church to travel to Cuba when he pays an official visit to the communist state in September.
Cuba's relations with the European Union have also improved recently as EU foreign policy chief Federica Mogherini visited Havana in March.
