The accident occurred on highway 4020, about 500 metres from Central Festival.
A witness said the Toyota Vios driven by the group of Russians crashed side on with a telegraph pole. It was not clear what caused the driver to collide with the pole.
A female died instantly at the scene, and a man died later at Phuket International Hospital.
The other passengers, Fawaz Mubark and Alyna Klimoea, are still in Phuket International Hospital.
Police have not yet released the names of the two deceased.
It is not known whether the group were expats or tourists.