The accident, involving four vehicles and one tractor-trailer happened just before noon Friday, roughly 15 km east of Lytton.
"The highway is shut down in both directions at this time with no estimated time when it will re-open. Our members are at the scene dealing with that collision at this point," said RCMP Sgt. Rob Vermeulen.
Vermeulen said it is unclear whether or not road conditions were a factor in the crash.
An avalanche on the Coquihalla Highway yesterday has shut down that route.
As an alternate route, Drive BC recommends taking Highway 3 to Princeton, then Highway 5A to Merritt or Kelowna with an additional travel time of 90 minutes.