Officials with the Ministry of Transportation said the boulder landed on the road near the seven mile marker, about 10 kilometres north of Lytton.
A geotechnical engineer is expected to assess the situation on Monday morning. Ministry officials have not provided an estimated time for when the highway will re-open.
Earlier this month a crash in the area on Highway 99 north of Lillooet killed two people and injured three others, leading to calls for improvements on the route.
Drivers can check DriveBC for updates.
Google Maps: Highway 12, B.C.
Instagram: B.C. Ministry of Transportation