Fire brigade officials said at least four people were confirmed dead and at least seven of about 30 injured are in a serious condition.
"We fear that many more are trapped under the four wagons. We cannot say what condition they are in," said Fire Brigade chief Andreas Kois, according to Reuters.
Police said at least 20 people were injured.
The train was travelling from the north-eastern city of Alexandroupolis to the port of Thessaloniki when it hit a truck attempting to cross the tracks near the town of Drama.
Two wagons derailed and two overturned, said Mr Kois.
State television showed pictures of dozens of rescue workers trying to enter the collapsed coaches as several ambulances were loading up the injured.
Police said the truck driver apparently ignored a warning bar at the crossing and was struck by the train at 8.50pm local time (3.50am AEST).