The accident happened on the main Ballynahinch to Carryduff Road.
The man was whisked from the scene by ambulance to the Royal Victoria Hospital in west Belfast.
A second person is also in hospital and is in a stable condition.
The road was closed while the PSNI’s Collision Investigation Unit examined the scene to try and determine how the crash happened.
Police say the road re-opened at 4.10 am this morning, Thursday, April 7.