East Sussex Fire and Rescue Service confirmed firefighters were called to the blaze in Beach Road, Newhaven just after 9.30am.
Residents have been asked to avoid the area and keep their doors and windows closed.
A fire service spokesperson said: "More than 80 999 calls have been made to us.
"The building has been evacuated. There are no reports of injuries.
"As of 11.30, 12 fire engines are being supported by water carriers and aerial appliances.
"It is too early to say what caused the fire.
"Sussex Police are among the other agencies supporting at the scene and in the local area.
A large cloud of black smoke was reportedly seen from as far away as Lancing in West Sussex.
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