The accident happened on State Highway 1, near the Henley-Berwick Rd intersection, about 11.30pm.
It appeared two cars had collided, one of which ended up down a bank beside the road.
St John staff confirmed a petrol tanker was also caught up in the crash.
One person with serious injuries, and three others with moderate injuries, were taken to Dunedin Hospital by ambulance, the St John spokeswoman said.