The green Mitstubishi pick-up was travelling south on the A9 when the incident happened at the Pass of Killiecrankie, near Pitlochry, at around 4pm yesterday.
The girl suffered head injuries and was airlifted to Yorkhill Children's Hospital in Glasgow where her condition is described as serious.
A 13-year-old boy and 27-year-old woman who were also in the vehicle were taken by ambulance to Ninewells Hospital in Dundee.
Their condition is not thought to be serious. The three people are thought to be members of the same family.
The southbound carriageway was closed until 10.30pm to allow for crash investigations to be carried out and the vehicles to be recovered.
Police Scotland are appealing for anyone who saw the incident or who might have seen the Mitstubishi and caravan travelling on the road before the collision to contact them on 101.