The train was carrying around 280 passengers when it derailed during the accident near the town of Soure at around 3:30 pm (1430 GMT).
The civil protection authority tweeted that 30 people were also slightly injured.
Portugal's President Marcelo Rebelo de Sousa said in statement that he offers "his condolences to the families and friends of those killed" after this "serious accident".
The Alfa Pendular high-speed train was travelling from the capital Lisbon to the northern city of Braga, stopping on the way at the cities of Porto and Coimbra.
Some 170 rescuers and two helicopters were quickly deployed to the crash site.
Source: AFP