Since the characteristics of thermal environment in the automobile cabin are different from those inside a building, it is very important to provide thermal comfort to the driver by making use of the driver’s physiological signals according to the cabin and vent exit temperature during driving in order to provide a comfortable environment. In this study, the brain and pulse wave signals of subjects were measured and analyzed under full load condition of the HVAC system in cooling and heating modes in a car cabin, when the inside temperature was changed from an uncomfortable level to a comfortable temperature range. When the HVAC system of the vehicle was operated in the cooling mode, maintaining the cabin and vent exit temperatures at 27.5°C and 11°C, respectively, was effective in increasing the activity of the autonomic nervous system and decreasing the driver’s stress during driving. In addition, maintaining the cabin and vent exit temperatures at 30°C and 13°C, respectively, was quite effective in increasing the concentration during driving. In the heating mode, the driver’s stress could be reduced when the cabin and vent exit temperatures were maintained at 22.5°C and 40°C, respectively. Besides, maintaining the cabin and vent exit temperatures at 20°C and 37°C caused an increase in concentration during driving. It can be inferred from these results that the environmental condition inside a vehicle is different from that inside a building, and that the vent exit temperature has a major influence on thermal comfort and concentration of the driver.