Firefighters have rushed to the scene in Paris to attend the blaze.
Footage on social media shows the huge cloud of smoke rising above the station.
The centre of the fire is understood to be near Gare de Lyon rather than inside.
Paris police have tweeted to say they are evacuating people from the area.
According to French news channel LCI, protesters had gathered in the area ahead of a concert at the nearby AccordHotels Arena in the Bercy neighbourhood.
Congolese artist Fally Ipupa is performing there this evening and Paris police announced on Friday morning one arrest had already been made near the convert venue.
The police’s statement said: “The concert by the Congolese artist Fally Ipupa takes place amid a particularly tense political context between supporters and opponents of the regime in the Democratic Republic of the Congo.
“The music event is provoking a growing reaction on social media and notably there have been several calls to protest the concert hall with the intention of fighting among spectators.”