The van, believed to be a Toyota Hiace, ended up down a bank after leaving the highway just past a tight corner at Queensberry, about 10km south of Luggate, about 12.45pm.
In a statement, police said there were seven occupants in the van when it crashed, and one person died at the scene.
Emergency services have freed two trapped occupants. The remaining occupants were able to remove themselves from the vehicle and are being treated by ambulance staff.
A St John spokesperson said two people were airlifted to Dunedin Hospital with serious injuries, while three others were taken to Dunstan Hospital, two with moderate injuries, one with minor injuries.
Police advise that the road is now open in one direction but motorists should expect delays.
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Motorists should expect delays and are asked to plan any travel accordingly.
The death brings the Easter road toll to two after a vehicle ran off the road and crashed into a tree in a rest area on State Highway 77 at Methven in Canterbury earlier today, killing the driver. No one else was in the vehicle.
