Emergency services were called to the scene in Truganina about 11.25am, following a crash involving a car, truck and a regional V/Line train.
Ambulance Victoria confirmed to 9News a number of people had been assessed at the scene, with one patient identified.
Hopkins Road in Rockbank is closed and motorists have been asked to avoid the area.
The closures are under Victoria Police control.
The road will reopen and services will resume when investigations are complete.