Two girls were hurt after being "struck by a saloon car while crossing the road" in Marton, police said.
One, aged 12, was knocked out and airlifted to Alder Hey Children's Hospital in Merseyside suffering from "major trauma", a spokeswoman for the North West Ambulance Service (NWAS) said.
Police said her condition was later given as stable, with her injuries no longer believed to be life threatening.
The second girl, 11, was taken to Blackpool Victoria Hospital with minor cuts and bruising, the NWAS spokeswoman added.
Emergency services were called to the scene, outside Tesco Express in Marton Drive, at around 2.13pm on Saturday.
An investigation was launched and the driver of the car involved, an Alfa Romeo Mito, was helping officers with their enquiries.
She is a 25-year-old woman from Preston.
Police said the girls were on the pedestrian crossing at the time of the collision.
Sgt Rob Gomery said: "Two girls have been injured, one seriously, and we want to establish exactly what happened.
“If you witnessed the collision, or have dash cam footage which could help us, please come forward.”
Anyone with information can contact police on 101 quoting log 0838 of October 6.