Halifax Road was closed by South Yorkshire Police earlier after a pedestrian was seriously injured in a collision with a car.
The man, in his 30s, was struck by a black Audi A3, close to the turn for Sainsbury's, Hillsborough, at 6.10am.
He was rushed to hospital with 'potentially life threatening injuries' and is reported to have undergone surgery.
The windscreen of the car involved in the collision was shattered during the incident.
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Police collision investigators have concluded their enquiries at the scene and the car involved has been towed away.
Bus company First South Yorkshire said there are delays of around 90 minutes on its services in the area.
A South Yorkshire Police spokesman said: "Emergency services were called to Halifax Road, Sheffield, just after 6.10am this morning, following reports of a collision.
"A black Audi A3 was involved in a collision with a pedestrian, close to the turning for Sainsbury’s.
"The pedestrian, a man in his 30s, has been taken to hospital with potentially life-threatening injuries."
Witnesses should call South Yorkshire Police on 101.