Officials say the two-vehicle crash happened just before 11:30 a.m. PT Sunday near Whittaker Road, between Victoria and Duncan.
Officials say two of the injured were flown to hospital in Victoria in critical condition.
Malahat Fire Department chief Robert Patterson, who lives about 100 metres from the crash site, heard the impact and arrived to find a pickup truck and a small car in pieces.
"I got there and the front of the car was pretty much under the truck and the back half of the car was about 20 feet away," he said.
"The damage is absolutely complete. About the only thing you can recognize from the car would be the spare tire on the back."
Barb McLintock with the B.C. Coroners Service said investigators are on scene and although there's no indication yet what caused the crash, there was a torrential downpour in nearby Victoria at the time.
The victims' names have not been released.
The highway has been closed in both directions for most of the day and likely will not reopen until about 6:30 p.m. PT.