A man has been killed and a woman has been seriously injured in a house fire in Adelaide's south.

Firefighters were called to a home on Amsterdam Road at Hackham West just before 8:30am on Saturday.

They arrived to find flames and smoke coming from the front room.

The Metropolitan Fire Service confirmed firefighters pulled the 61-year-old man out of the burning property but he died at the scene.

The 46-year-old woman escaped through the front window and was taken to the Flinders Medical Centre with life-threatening injuries.

"We arrived with our vehicle and found a woman who had escaped from the fire and we started first aid on her and did fire control," MFS Commander Wayne Trezise.

"We then proceeded inside the premises and unfortunately found a person on a bed inside and we removed that person and placed them in the care of ambulance [officers].

"The injuries were quite bad, lots of lacerations on the woman and some burns and the man had burns."

Two cats and two dogs were also killed in the fire.

About two dozen firefighters took 15 minutes to extinguish the blaze.

The cause of the fire is undetermined and the damage to the house is estimated at $200,000, a MFS spokesperson said.

Neighbour Pamela Jenkins said she could see smoke and flames at the property from her bedroom window.

She said when she got to the burning house, firefighters carried a person out and tried to resuscitate them.

Another neighbour, Kevin, said he heard an explosion from his home.

"I thought I heard something, looked out my window, saw a neighbour running down the road and the house went up," he said.

"All we saw was smoke and the house went up, then the fire brigade and ambulances rocking up."

The road has been closed near the scene, and police are asking pedestrians and drivers to avoid the area.