Three people have died after a fierce fire erupted inside a home in Sydney's south-west this morning.

Four people, and two firefighters, were taken to hospital after the blaze broke out on Rottnest Avenue, Hinchinbrook about 5:30am today.

A team of 60 firefighters battled the flames while paramedics treated occupants at the scene.

Six people were inside the home. Three were rescued from the burning building by firefighters.

Two women, believed to be aged in their 40s and 60s, were pronounced dead at the scene.

A boy, 10, was rushed to Westmead children's hospital in a critical condition but died later on Sunday morning.

Another three people managed to escape the home themselves.

A man in his 40s and a woman in her 60s were taken to Concord Hospital where they are in a critical condition and stable condition respectively. 

Another woman, aged in her 30s, was taken to Liverpool Hospital in a stable condition.

Superintendent Luke Unsworth, from Fire and Rescue NSW, said crews arrived to find a "very intense house fire".

"The fire was so intense that firefighters actually couldn't make it to the front door because of the radiant heat," he said.

"They made their way up onto the second storey, and at that location managed to rescue three people who were handed over to ambulance for treatment.

"Unfortunately, two of those three people have been confirmed to be deceased … which is a tragic outcome for both the family and the local community."

Fire crews managed to stop the fire from spreading to neighbouring homes.

Two firefighters were also injured while fighting the blaze, with one suffering an electric shock and the other falling through a weakened second-storey floor.

Both were taken to hospital for treatment.

A neighbour attempted to enter the home and doused it with a garden hose but it had little impact due to the intensity of the fire.

Superintendent Unsworth said winter was a "significantly dangerous time" for house fires, with 13 deaths recorded this season already.

Fire and Rescue Deputy Commissioner Megan Stiffler said there had been 500 house fires so far this winter.

"We've lost 13 lives due to home fires this year and that's nine more than the whole winter season last year," she said.

Deputy Commissioner Stiffler said half of the homes impacted by fire this year did not have working smoke alarms, and stressed their importance to fire safety.

Dominic Carr from NSW Ambulance said paramedics treated eight patients, including two firefighters, at the scene.

He said paramedics worked to resuscitate the boy who had suffered critical injuries.

"Look, it's never easy. You get there you give it your best go. You try everything you can," he said.

"We did everything we could. The hospital was waiting for us. They dd everything they could. Unfortunately, the child succumbed to their injuries."

Detective Chief Inspector Alyson Fenwick said an investigation into the cause of the fire was underway.

"This is a traumatic situation that has occurred and they [the family] will be well supported," she said.

Chief Inspector Fenwick called for anyone with information about the fire to contact Crime Stoppers.

Superintendent Unsworth said it was likely the building had a smoke alarm, and whether or not it was functional would form part of the investigation.