It happened about three kilometres west of Edgeley, Sask. at a level crossing around 12 p.m. Thursday about one kilometre north of Highway 364.
Police say the truck was driving southbound and was hit by the eastbound train at a level crossing.
The man was declared dead at the scene. No other injuries were reported to police.
A spokesperson for Canadian National Railway says about 18 rail cars left the tracks, which caused a small spill of an unknown substance.
Mounties say initial reports suggest some fuel may have leaked.
The spokesperson says there are no reports of any fires.
The derailment’s cause is being investigated.
RCMP, CN police and environmental experts remain on the scene.
Officers have blocked off the area and are asking people to avoid it.