Abstract: Advancing into the Earth’s deep subsurface is a critical scientific and technological challenge that must be addressed. Heat-related hazards caused by high geothermal gradients in deep coal mining are becoming increasingly severe, posing significant threats to workers’ health and mine safety. Air enthalpy, as an important indicator in mine cooling design, has the potential to become an indicator for thermal environment evaluation. A simulation platform was established to replicate high-temperature and high-humidity mine environments. Experiments were conducted to assess human physiological and psychological thermal responses under various conditions. The effectiveness of coupled temperature-humidity indices in characterizing human thermal responses was analyzed. The functional relationships among air enthalpy, exposure duration, and physiological indicators were investigated. A classification scheme for thermal environment evaluation was proposed. A thermal environment evaluation model based on air enthalpy was developed. The model was applied to the engineering design of mine shaft cooling systems. High temperature and humidity cause rapid increases in physiological indicators, often exceeding safety thresholds. High humidity, in particular, exacerbates thermal discomfort. Physiological and psychological responses are influenced by the interaction of temperature and humidity. Correlations between thermal environment indices and thermal responses follow the order: air enthalpy > temperature > wet-bulb temperature > humidity. The relationship between air enthalpy, exposure time, and thermal responses fits a Logistic Cumulative model. Based on physiological safety thresholds, the mine thermal environment is classified into four levels: comfort, safety, danger, and limit. For the “three-eight” work system, air enthalpy limits are set at 67.923, 80.519, and 98.944 kJ/kg for different safety levels. A mine thermal environment evaluation model was established based on the standard enthalpy-humidity diagram. The thermal safety enthalpy threshold was applied in designing the cooling system for Pingdingshan No.10 Mine and the system’s cooling load was calculated at 2 000 kW. After implementation, the working face environment improved from thermal limit to thermal safety level. Monthly output increased by 120 000 tons following temperature reduction, yielding substantial safety and economic benefits.