The incident took further down the rails from where two other anti-nuclear protesters had earlier chained themselves to the tracks near the town of Nancy, briefly delaying the train, rail officials said.
Paramedics quickly cared for the protester after the incident near the town of Avricourt, but his leg was severed and he died en route to a nearby hospital, the police official said on condition of anonymity. The official said at least one other protester had been injured.
According to an early investigation, Sebastien Briat, a 21-year-old protester from the nearby Meuse region, died from injuries sustained when he and other activists were surprised by the train as they prepared to chain themselves to the rails, police officials said.
The train's driver braked suddenly but was unable to avoid hitting the protester, the officials said.
About 12 miles up the rails in the town of Laneuveville-devant-Nancy, police intervened to cut the chains that two protesters from activist group Sortir du Nucleaire (Out of Nuclear) had used to lock themselves to the tracks, officials from railway authority SNCF said.
The train was delayed for about two hours, before continuing its route from a reprocessing plant in western France to a rail terminal in the German town of Danneberg. It was carrying 12 containers of waste destined for a storage site in nearby Gorleben.
At least 4,500 people demonstrated Saturday at the radioactive waste way station in Gorleben, part of regular protests over concerns that the nuclear material is unsafe.
Spent fuel from Germany's nuclear power plants is sent to France and Britain for reprocessing under contracts that oblige Germany to take back the waste.
Some previous shipments of radioactive waste to Gorleben have drawn thousands of protesters and led to clashes with police.
The demonstrations have faded, however, as the German government last year embarked on a plan to phase out nuclear power altogether and close its remaining 18 nuclear power plants by about 2020.