Air-conditioning equipment is used in various places such as houses, office buildings, and public facilities and is indispensable in modern-day life. Therefore, the energy consumption of air-conditioning equipment accounts for a large percentage of the total energy consumption in the average household. Specifically, it accounts for 26% of the annual energy consumption in ordinary homes and 27% in industry, according to the Annual Energy Report for Japan, which was presented by the Ministry of the Economy, Trade, and Industry, and the Agency for Natural Resources and Energy in 2010. Therefore, it is desirable to reduce energy consumption by reducing the air-conditioning load. The Ministry of the Environment recommends a constant preset temperature of 28°C in summer to decrease energy consumption. However, many people feel uncomfortable in such a thermal environment. Thus, an air-conditioning control to simultaneously suppress energy consumption and maintain human thermal comfort is desired. To develop such a control, an index to accurately evaluate human thermal comfort is needed. When a person feels comfortable or uncomfortable, their prefrontal area, which is involved in thinking and the feeling of emotions, is activated. It is presumed that the measurement of the brain activation reaction of a person will reveal whether the person feels comfortable or uncomfortable in the thermal environment. The evaluation of thermal comfort by means of brain activation reactions will allow one to develop the optimum air-conditioning control to maintain human thermal comfort. This paper proposes a method to evaluate thermal comfort via brain signals and ultimately aims to develop an air-conditioning control system utilizing this evaluation method. This paper will describe the measurement procedure of brain activation reactions to indoor-temperature change by using near-infrared spectroscopy and the relationship between thermal comfort and brain activation reaction. This study also investigated the changes in oxyHb levels together with indoor-temperature changes, measured with the NIRS. We measured the changes in the oxyHb levels of the prefrontal area when the temperature increased and decreased. As a result, the oxyHb level in the prefrontal area correlated with the indoor-temperature change, the PMV, and the subjects’ declaration of thermal sensation. Conversely, the change in the oxyHb level with the inclusion of wind and a constant indoor temperature significantly differed with that with a varying indoor temperature. Furthermore, the oxyHb change correlated with the PMV and the subject’s declaration of thermal sensation. Therefore, the measured oxyHb change may represent the thermal comfort of a person.