The incident happened on the A6091 near Borders General Hospital at around 9.30am today (Wednesday).
Police say they received a report of a head on collision involving a silver coloured Vauxhall Vivaro van and a red DAF articulated lorry.
Emergency services attended and the 42-year-old van driver was pronounced dead at the scene.
The 53-year-old lorry driver was taken by ambulance to the Royal Infirmary of Edinburgh with serious injuries.
A report will be submitted to the Procurator Fiscal.
Sergeant John Lang at the Road Policing East said: “We have spoken to several people already who have witnessed this crash but are still keen to speak to anyone else who witnessed it and have not yet spoken to police.
“Anyone with information can contact police via telephone number 101 quoting incident number 0736 of September 1 2021.”