The coach overturned while driving on the road linking the city of Baracoa, near Cuba's eastern tip, to the capital Havana. The region is mountainous with winding roads.
Five are also in critical condition after the bus, carrying tourists from a few countries including Canada, lost control on a highway in the eastern part of the country.
Officials were working to identify the dead.
CNN's Patrick Oppmann reported from Havana and Hira Humayun from Atlanta.
"Global Affairs Canada is aware of reports of a bus crash in Cuba involving foreign tourists".
No emergency declaration to end US govt shutdown
Representative Mark Meadows, a North Carolina Republican, has also suggested using that money or other discretionary fees. Donald Trump now holds the record for presiding over the longest US Government shutdown in history at 22 days.
First dose of winter weather in 2019 on its way
Areas around Effingham have already seen significant snowfall amounts, like the measurement below near Beecher City of 7.5 inches. Saturday, temperatures registered at 30 degrees ad freezing fog was reported in some areas.
Nobody is guaranteed World Cup flight to England says Rohit Sharma
Vice-captain Rohit Sharma Thursday said India's World Cup squad is more or less settled but nobody should take his place for granted as poor form could lead to omissions.
Some 33 people were injured, including citizens from the United Kingdom, the US, Canada, France, the Netherlands and Spain.
A Frenchman and a German woman were also among the four tourists killed in the accident, along with three Cubans, the Venceremos newspaper said.
According to Radio Guantanamo, two Canadians were injured - a 56-year-old man and a 54-year-old man.
While the extent of all the injuries from the latest crash isn't known, media in Cuba confirmed that of the 40 passengers on board, the 33 surviving people were all taken to a hospital in Guantanamo for treatment of their injuries. Past year in all of Cuba there were over 11,000 auto accidents on their poorly-conditioned highways. Thursday's wreck was the fourth major bus accident in a month.