Fifty firefighters are tackling a large blaze at Nottingham station.
The building was evacuated and no injuries have been reported.
Trains will not be stopping "until further notice", a spokesman for East Midlands Trains said.
Nottinghamshire Fire and Rescue Service tweeted: "There are now 10 fire engines in attendance approximately 50 firefighters fighting the fire at the #NottinghamTrainStation".
Nottinghamshire Police said surrounding roads are closed.
The force tweeted: "Station Street, Carrington Street and Queen's Road have been closed. Transport in the area will be severely disrupted."
A spokeswoman for East Midlands Ambulance Service said it is aware of the incident.
"We have a clinical manager and specialist paramedics at the scene," she said.
Travel disruption information posted on the East Midlands Trains website said: "At present we do not have a firm estimate as to when the station will be able to re-open; however, we expect trains to be disrupted on all routes through Nottingham for the whole of Friday 12th January."