People have been urged to avoid the area after a huge van explosion outside Westquay.
A fire engulfed a van on Harbour Parade just after 9.30am, before an explosion and a huge fireball rose into the sky.
A plume of black smoke was seen across the city.
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Hampshire Fire and Rescue Service rushed to the scene, with scores of firefighters tackling the blaze for more than an hour.
They've asked people to avoid the area.
In a statement, a spokesperson said: "Crews from St Mary’s, Redbridge and Hightown are currently in attendance at a vehicle fire following reports of smoke and flames at the back of Westquay, Southampton at just after 9.30am this morning.
"People are asked to avoid the area while emergency services deal with the incident. Harbour Parade is closed in both directions."
Westquay itself has been evacuated with staff and customers currently forced to wait outside.
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