
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.
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 7:50 p.m, but reported an emergency at 5:42 p.m. 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 mobilized doctors and emergency workers in the rural area, which is about 220 miles (350 kilometres) 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."
State media gave no details on what happened to the airliner, saying only that the cause of the crash was being investigated.
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 on Friday.
Cuban media said earlier that flights and train service 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.