Around 60 firefighters are tackling a huge blaze in the new section of Nottingham station.
The fire broke out in the main concourse early on Friday and spread to the roof.
The scene was evacuated and no injuries were reported, emergency services said.
A spokesman for Nottinghamshire Fire and Rescue Service said at least 60 firefighters were at the scene, along with 15 appliances.
He added that a crew from Ilkeston in Derbyshire was assisting.
Bryn Coleman, head of prevention at Nottinghamshire Fire and Rescue, told BBC Breakfast that crews arrived at 6.30am to a “significant fire in the new section of Nottingham train station”.
He said: “Unfortunately, the fire is spreading to the roof of the new section of Nottingham train station, and is now travelling along the concourse of the area across the main lines into Nottingham train station.
“We’ve got in the region of 60 firefighters currently here at the scene, and we are fighting the fire from inside the building using breathing apparatus, hose reels and jets.”
The blaze has caused disruption across the local transport network and several cordons and road closures are in place.
Nottinghamshire Police said all trains are cancelled and advised people to avoid the area where possible.
The fire disrupted the journeys of many airline passengers booked on flights to or from East Midlands Airport.
Trains to the airport from Nottingham, Lincoln and Leicester were cancelled on Friday morning.
East Midlands Trains advised people not to travel “unless it is absolutely necessary” and said trains “cannot run to/from Nottingham”.
Travel disruption information on the company website said: “There is a fire at Nottingham station. This is disrupting our trains on the Nottingham/London St Pancras Matlock/Nottingham/Newark, Nottingham/Mansfield/Worksop, Leicester/Lincoln/Grimbsy, Nottingham/Grantham/Skegness and Liverpool/Nottingham/Norwich routes.”
(Matthew Vincent/PA)
Bryn Coleman, Incident Commander at the scene for Nottinghamshire Fire and Rescue Service, said: “We have a serious fire at the concourse and the walkways of Nottingham station.
“We got a call at approximately 6.30am to a fire involving a toilet block – that has now spread to the roof void.
“It is quite a complex construction. We have 12 fire appliance units here, plus specialist firefighting equipment.
“The conditions inside the station at this time are quite arduous for our firefighters, who are committed and working really hard inside.
“The early indications are that it will remain closed for the rest of the day.”
Mr Coleman said they were working with colleagues from Network Rail and East Midlands Trains in a bid to reopen the station, but added that at the moment “there is still a significant firefighting operation taking place”.