The crash happened at about 1am yesterday on the M8 in West Lothian, about one mile east of Harthill, on the eastbound carriageway.
Lothian and Borders Police said the carriageway, the main route between Glasgow and Edinburgh, was closed for several hours.
The collision involved a Fiat Stilo and a MAN HGV.
Police officers said there are initial reports the Fiat was travelling west on the eastbound carriageway, having joined it at junction 3A, before it collided with the HGV, which was heading east.
A 19-year-old man from Bathgate who was driving the car died at the scene, while the 39-year-old lorry driver was not injured.
The eastbound carriageway of the M8 was closed between junction five, Shotts, Lanarkshire, and junction four, Whitburn, for around five hours while investigations were carried out at the scene.
Inspector Richard Latto said: “At the moment, we are working to establish the circumstances leading up to this collision, and would appeal for anyone who may have been in the area at the time, and who may have seen what happened, to contact police.”