The 30-year-old suffered a head injury in the collision, which happened in the early hours of yesterday.
Police Scotland said the pedestrian was hit by a Vauxhall when he was walking along John Knox Street, near Wishart Street, at around 3.45am.
The 48-year-old car driver contacted emergency services. He was not hurt but is said to have been left very shaken by the incident.
The man who was hit was initially taken to the nearby Glasgow Royal Infirmary but was later transferred to the Southern General Hospital. Medical staff say he is in a serious but stable condition.
Police are asking any witnesses to the crash to come forward.
Sergeant Jo McPherson, of the roads policing complex, said: "Despite it being in the early hours of the morning, this route can often be busy with taxis and cars as people make their way out of the city centre.
"Officers from road policing are appealing to anyone who may have been in the area around the time of the incident to come forward. The area is also overlooked by residential flats and it's possible someone may have witnessed the crash from their flat.
"If you have any information, please contact officers on telephone number 0141 532 6443."