The Golden Highway is closed in both directions at Cassilis due to a multi-vehicle crash at Thompson Road.
Motorists are advised to avoid the area.
Motorists already on the highway are advised to allow plenty of extra travel time and follow the directions of emergency services on site.
Emergency services are working to free several people trapped in the vehicles.
Two medical helicopters are also attending, as well as traffic crews.
For the latest traffic information, visit www.livetraffic.com or download the Live Traffic NSW app.