A seven-year-old girl is fighting for life following a horrific crash south of Sydney that killed her mother and twin brother on their way to school.

Emergency services were called to the Hume Motorway near Wilton, south of Sydney, at about 7.50am on Tuesday after two cars were involved in a head-on crash in the south-bound lanes, about one kilometre south of the Picton Road turn-off.

Witnesses have reported seeing a Holden Astra travelling north before veering across the median strip and hitting a Mazda four-wheel drive travelling south-bound.

The Mazda was being driven by 49-year-old mother Julie Bullock, who was taking her twins Sienna and Hudson, both 7, to school at Wollondilly.