Emergency services were called to Northcote Plaza, on Separation Street, about 10.50am on Thursday after a car drove into the Suzanne Grae clothing store.
The car crashed through the shop and into the middle of the shopping mall, with video footage showing dozens of shoppers inside at the time.
Police said the vehicle struck six pedestrians and the driver, who suffered non life-threatening injuries, is assisting with their inquiries.
Police said the incident "is not being treated as deliberate".
Paramedics assessed six people at the scene, with four taken to hospital.
A man was treated for upper body injuries and has been taken to the Royal Melbourne Hospital in a serious but stable condition.
A man and woman were taken to the same hospital in stable conditions, while a woman was taken to St Vincent's for observation.
Another two people were assessed at the scene, but not taken to hospital.
The shopping centre has been partially evacuated to allow for structural assessment.
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