A number of fire appliances, including the VEMA aerial machine, have been containing the blaze
The PSNI said: "Due to a fire at a nightclub, Strand Road, Derry/Londonderry is closed from Lawrence Hill to Asylum Road. Foyle express way is also closed.
Cordons are in place between Lawrence Hill and Asylum Road and Queen's Quay has also been sealed off.
"Motorists and pedestrians are asked to avoid the area.
"A number of premises have been evacuated.
"Anyone living or working in close proximity to Strand Road is asked to ensure they keep their windows closed."