Jessica McMurray was last in contact via phone on Saturday and police believe she remains in the Hamilton area.
However, the 14-year-old has not been seen in person since Wednesday and her family's concerns are growing.
Sergeant Stewart Dyer, Hamilton Police Office, said: "Jessica has her phone with her and was last in contact around 1pm yesterday, however, since nobody has seen her in person since
Wednesday, we are growing increasingly concerned for her.
"We are appealing for anyone with any information on her whereabouts to get in touch with us as soon as possible.
"Jessica, we would also ask you to get in touch with us or your family to let them know where you are and that you are okay."
She is described as being around 5ft 4ins with long brown hair.
The teenager was last seen wearing a black coloured jacket and black coloured leggings.