Police confirmed the fatal crash took place around 4.50pm yesterday on the northbound carriageway of the M74 at Lockerbie.
The 52 year old man was travelling as a passenger in a Vauxhall Combo, with a 33 year-old male driver, when it hit a Mercedes Actros articulated LGV near a junction.
Emergency services attended and the 52 year-old was pronounced dead at the scene.
The driver of the van was taken by ambulance to the Western General Hospital in Edinburgh where he is being treated for his injuries. Hospital staff describe his condition as serious.
The driver and male passenger in the Mercedes lorry were uninjured.
The Irish Post has learned that the deceased is Irishman Paul Brown.
Mr Brown was a Celtic fan and is believed to have worked in construction. He lived in the Irish stronghold of Coatbridge, east of Glasgow.
He was born in Derry but has lived in Scotland for many years.
His brother is travelling from Ireland to Glasgow to formally identify the body.
The family believe the body will be back in Derry by Wednesday.
Sergeant Peter Forsyth from the Road Policing Department in Lockerbie is urging any witnesses to the crash, or anyone with information that may assist their investigation to contact Police Scotland on 101.