The woman, aged in her 20s, was struck by a truck at the corner of Elizabeth and Lonsdale Streets after 4.30am (AEDT), police say.
Ambulance Victoria said she suffered serious injuries and was taken to the Royal Melbourne Hospital.
A hospital spokeswoman said the woman's condition was critical.
The truck driver did not stop at the scene and police are reviewing CCTV footage in the area.
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