The Otago Daily Times understands there are children among the injured.
Police were called to the scene, on State Highway 1 between the intersections with Titri and Bungards Rds, about 12.15pm.
A police spokeswoman initially said "reports suggest there are serious injuries".
Two - one critical and one serious - were taken by helicopter and the other two by ambulance.
Earlier, St John said three ambulances and two helicopters had been sent to the scene.
"I didn't see it happen, but it looked horrific," she said.
"I don't know how it would have happened as it was right on the brow of the hill, so no one should have been considering passing."
A Fire and Emergency New Zealand spokesman said three appliances from Milton, Waihola and Balclutha responded.
State Highway 1 between Bungards Rd and Titri Rd was closed. A reporter at the scene said traffic was being diverted down Titri Rd.