The 29-year-old was walking on Cruachan Road, near to its junction with Slenavon Avenue, Rutherglen, when the attack happened.
At about 9pm on Thursday he was approached by a man who seriously assaulted him with a bladed weapon.
He was taken by ambulance to Queen Elizabeth University Hospital where he is being treated for a stab wound.
Hospital staff described his condition as serious.
Detective Constable Stephanie Bertram of Cambuslang Police Office said: “I would appeal to anyone who was in the area of Cruachan Road and Slenavon Avenue around 9pm on Thursday evening who witnessed any disturbance or anyone acting suspiciously to come forward.
“Inquiries are being carried out in the area and officers are viewing CCTV footage to gather more information on the suspect.”
The suspect is described as white, of slim build with short brown hair.