South Yorkshire Fire and Rescue said one casualty was rescued from a burning building on Chesterfield Road, Heeley, and taken to hospital.
An air ambulance was seen landing on the car park of the nearby Heeley Retail Park.
The fire involves Milan’s Pizza takeaway, which has flats above.
In a statement, the fire service said: “Seven fire engines and a turntable ladder are responding to a serious fire involving premises on Chesterfield Road in Sheffield.
“Firefighters were called the the incident at around 10.30am.
“One casualty has been brought out of the premises and has been taken to hospital by ambulance.
“Fire crews are searching the premises for further casualties.
“People should avoid the area if possible.
“The fire is thought to have started at a takeaway which also has residential flats above.
“An investigation into the cause will begin once the fire has been extinguished.”