Spanish railway company Renfe confirmed the train had come off the tracks near the city of Santiago de Compostela in the Galicia region.
A Renfe spokesman told AFP news agency several people had been killed and several more injured.
Spanish news agency Efe quoted police and hospital sources as saying at least 50 people were injured.
Reports said all 13 carriages had left the tracks, and four carriages had overturned completely.
Images showed dozens of emergency workers crowded around ruined carriages.
Passengers were shown lying on the ground being treated.
Renfe said the train carried more than 200 passengers, and was on the high-speed route between Madrid and Ferrol on the Galician coast.
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