•Energy saving potential is assessed by energy balance and thermal comfort.•Enthalpy change is used as the result of energy fluxes of a room in hot-humid zones.•Thermal comfort index APMV is proper for naturally ventilated buildings.•Steps are given to design a well-performed naturally ventilated building. This paper examines naturally ventilated buildings in hot and humid summer zones and proposes an air enthalpy-based energy conservation rating method with an emphasis on the combined thermal comfort-ventilation parameters, particularly the impact of humidity and human adaptations on thermal comfort. The new method starts with energy flow analysis to a naturally ventilated room and assessment of thermal comfort accounting for the humidity of the naturally ventilated room as well as the occupants’ adaptability, differing from the PMV models and widely-used adaptive models adopted in existing rating methods. It contributes to designing a well-performed naturally ventilated building by analysing the interplay of climate elements, design features, indoor thermal comfort, and energy consumption for cooling in hot-humid climates. It also gives the access to rate the influence of an estimated energy saving due to natural ventilation on the energy system at a district or national scale. The proposed method is then applied to a naturally ventilated office located in three cities within this particular climatic region of China. The results indicate that natural ventilation is an effective way to improve thermal comfort while maintaining a low cooling energy consumption in hot-humid summer zones. Using natural ventilation could help reduce cooling energy demand by 10–30% compared to not using natural ventilation. Its energy saving potential is strongly affected by the enthalpy of outdoor air, followed by airflow rate. Then, a contrast comparison between the new method based on energy balance and Chinese indoor thermal comfort standard and the conventional method coupling adaptive ASHRAE standard-55 thermal comfort model with sensible heat balance model is carried out. The contrast results validate the considerable impacts of humidity on energy balance analysis and thermal comfort rating. It points out the new method makes improvement of the maximum energy saving potential of naturally ventilated buildings prediction.