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Local cooling has proven to be an alternative to traditional comfort air conditioning to ensure users' thermal comfort while conserving energy. Few studies have investigated the gender differences in the applicable cooling temperatures and the applicable cooling locations and the differences in the sensitivity of skin temperature to thermal sensation under local cooling. Based on the design of orthogonal experiment, nine chamber experiments were conducted through different combinations of ambient temperature, cooling temperature, and cooling location. The subjective questionnaires and objective measurements were obtained in each experimental case. The results showed that the ambient temperature and the cooling location significantly affect the human overall thermal sensation of both genders under local cooling, while cooling temperature and cooling location significantly affect the local thermal sensation. For female, a neutral thermal sensation can be achieved by cooling the back at 24-26 °C when the ambient temperature is 31 °C. Back cooling at 22-26 °C is effective for male when the ambient temperature is 28 °C and 31 °C, and sole cooling with a higher cooling temperature is more acceptable at 34 °C. Moreover, female skin temperature is more sensitive to thermal sensation than that of males under local cooling. The upper arm skin temperature is most sensitive to thermal sensations for female, while the forearm skin temperature is most sensitive for male., Competing Interests: Declaration of competing interest We declare no conflict of interest. This manuscript is approved by all the authors for publication. This work was supported by the National Natural Science Foundation of China (No.51878405)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)