The child was walking with his mother on Barnes Terrace in Ayr yesterday afternoon when he tried to cross the road.
As he did so, he was struck by the car just after 3pm.
Emergency services were called and the boy was airlifted to Glasgow's Yorkhill Children's Hospital.
The road was closed for some time as specialist officers carried out accident investigations.
Police said the woman driver of the car was not injured but was left "very upset" by the incident.
Sergeant Iain Pittams, from the divisional roads policing unit at Irvine, is appealing for anyone who was in the area at the time to get in touch.
In a statement, Police Scotland said: "Police are appealing for information following a road traffic accident on Monday June 2.
"Around 3.05pm, a four-year-old boy was walking with his mother on Barnes Terrace near to the junction with Barns Park in Ayr when he tried to cross the road.
"As he was crossing the road, he was struck by a car. Emergency services were contacted and the boy was airlifted to Yorkhill Children's Hospital where he is detained in what is described as a critical condition."