The train was travelling from the city of Alexandroupolis to the port of Thessaloniki when it hit a lorry trying to cross the tracks near the town of Drama on Sunday evening.
Police said at least four people were killed and 35 injured.
A senior fire brigade official said rescue workers were trying to free other passengers trapped in two carriages.
"We have not yet determined how many more casualties there are," he said.
Police said the truck driver had apparently ignored a warning bar at the crossing, 3km outside Drama, and was hit by the train at 8.50pm (1750 GMT).
It was the second train accident in northern Greece in a month. In March, three people were killed when another passenger train hit a car at a rail crossing.