AeroCaribbean Flight 883 went down near the village of Guasimal in Santi Spiritus province, carrying 61 passengers and a crew of seven.
Cuba's Civil Aviation Authority issued a statement early Friday saying there are no survivors.
A list of passengers indicates the dead include nine Argentines, seven Mexicans, three Dutch citizens, two Germans, two Austrians, a French citizen, an Italian, a Spaniard, a Venezuelan and a Japanese.
AeroCaribbean Flight 883 went down near the village of Guasimal in Santi Spiritus province, carrying 61 passengers and a crew of seven, state television said.
It said 28 passengers were foreigners, but did not give a breakdown of nationalities.
State media said the names of those on board would be released later.
Rescue workers were at the scene and had recovered the first bodies, according to the local state-run newspaper Escambray. It said they were also searching the rugged area for survivors.
A photo posted on the paper's web site showed a large piece of the plane in flames, with rescue workers in olive-green military uniforms standing around it.
It said the local Communist Party chief as well as Interior Ministry and other officials were at the scene helping with the rescue effort.
The twice-a-week flight goes from Port-au-Prince, Haiti, to Santiago de Cuba to Havana. It had been due to land in the Cuban capital at 7.50pm (local time), but reported an emergency at 5.42pm and subsequently lost contact with air traffic controllers.
State media said that the plane was an ATR-72 twin turboprop and that the crash site was not far from the Zaza reservoir, the largest in Cuba.
It said authorities had mobilised doctors and emergency workers in the rural area, which is about 350km east of Havana.
At Havana's national terminal, relatives of those on board the plane were kept isolated from other passengers and journalists.
"This is very sad," said Caridad de las Mercedes Gonzalez, who was manning an airport information desk. "We are very worried. This has taken us by surprise."
The flight would have been one of the last leaving Santiago de Cuba for Havana ahead of Tropical Storm Tomas, which was on a track to pass between Cuba's eastern end and the western coast of Haiti.
Cuban media said earlier that flights and train services to Santiago were being suspended until the storm passed.
AeroCaribbean is owned by Cuban state airline Cubana de Aviacion.
The last passenger plane crash on the island occurred in March 2002, when a Soviet-made biplane carrying 16 people - including 12 foreigners - plunged into a small reservoir in central Cuba. The plane was operated by a small local charter company called Aerotaxi.
