Personal cooling garments (PCGs) are important to help human body regulate its own thermal comfort under high temperature environments. This study focuses on the thermal comfort of personal cooling garment in high temperature environments, which is of great significance in the context of current climate warming and frequent extreme high temperature events. Traditional research on cooling garment mainly focuses on improving its cooling performance, but ignores how to improve human thermal comfort by optimizing cooling equipment and garment parameters. This study developed a semiconductor liquid cooling garment (SLCG) that can adjust and help the human body achieve optimal thermal comfort under different environmental conditions. Through computational fluid dynamics (CFD) simulation, this study established a human body model wearing SLCG to analyze the effects of parameters such as external ambient temperature, flow rate, and inlet water temperature on thermal comfort. Different from traditional research, this study proposed a heat exchange network design with non-uniformity layout, this layout accounted for the variations in heat dissipation across different regions of the human body, enabling targeted optimization of the cooling effect. The results show that among the five different pipe spacings, the spacing of 2–3.5 cm can most effectively improve human thermal comfort. Specifically, in an environment of 34 °C, the parameter combination of inlet water temperature of 24 °C and flow rate of 26 kg/h was selected; at 36 °C, the inlet water temperature was 22 °C and the flow rate was 40 kg/h; at 38 °C, the inlet water temperature was 20 °C and the flow rate was 54 kg/h. The accuracy of the newly developed numerical model was evaluated through a series of experiments. Validation efforts involved comparing the model’s numerical results with experimental outcomes derived from human trials. The error between the simulated and experimental temperatures at each inlet and outlet was confined to within 0.2 °C. The error of cooling power is within 8 %, which proves the accuracy of the numerical model and the rationality of SLCG optimal parameters. This study not only proposed a new SLCG design idea, filling the research gap on thermal comfort optimization in the field of cooling garment, but also provided a theoretical basis and practical reference for the future design of cooling garment in different high temperature environments.