Emergency crews responded to a fatal collision involving a truck on Bells Line of Road on Wednesday.
A police spokesman said a semi-trailer carrying sand was involved in a collision with two cars near Mt Tomah about 12.15pm.
A statement on Blue Mountains Local Area Command's Facebook page confirmed the collision was fatal, however it was unclear who had been killed.
"This is a fatal collision involving a heavy vehicle approximately four kilometres west of Mt Tomah," the statement said.
"Police and other emergency services will be in attendance at the location for some time during both the investigation and later recovery of the heavy vehicle."
A NSW Ambulance spokeswoman said four people had been treated at the scene.
"We're looking at four patients . . . two ambulance crews are on the scene," she said earlier this afternoon.
Bells Line of Road was closed in both directions while investigators examined the scene.
East-bound traffic was being diverted onto the Darling Causeway and back onto the Great Western Highway, while west-bound traffic was being turned around at the Mt Tomah Botanic Gardens.
Motorists had been asked to avoid the area and expect significant delays.