The collision occurred at 7.36pm on Monday, May 16 on the A61, Almsford Bank and involved a red Volkswagen Golf and a black Range Rover.
The Golf was travelling from Harrogate towards Pannal and the Range Rover was travelling from the Pannal direction towards Harrogate.
The sole occupant of the Golf was taken to hospital with serious, potentially life changing injuries.
The five occupants of the Range Rover were also taken to hospital with injuries.
Road closures were put in place for around six hours while emergency crews attended the scene and an initial investigation was carried out.
Anyone who witnessed either vehicle before the collision or who saw the events surrounding it is urged to contact North Yorkshire Police with information.
The police are also urging people to get in touch if they have any dash-cam footage that may assist the investigation.
Email [email protected] or alternatively you can call North Yorkshire Police on 101, select option two and ask for Paul Buckley.
If you wish to provide information anonymously this can be done by calling the independent charity Crimestoppers on 0800 555 111.
Quote reference 12220083726 when providing information.