The collision, involving a blue Peugeot 308 and a white Volvo lorry, occurred at around 7:15pm.
The male driver of the Peugeot died as a result of his injuries sustained in the collision.
The Belfast Road outside Ballynahinch was closed for a period of time, but has since re-opened.
Police are appealing to anyone who was travelling on the Belfast Road around this time who witnessed the collision, or anyone who saw the blue Peugeot prior to the collision to contact them.
Police are also appealing to drivers who have a dash cam fitted to their vehicle to check their footage.
Anyone with information is asked to call police on the non-emergency number 101, quoting reference number 1100 of 26/04/18.