Fluctuation in the hygrothermal environment can facilitate the deterioration of cultural relics in the Maijishan Grottoes. The purpose of this research is to develop a hygrothermal simulation model of grottoes to analyze the changes in the hygrothermal environment under different influencing factors. First, the temperature and relative humidity (RH) in Cave 101 of the Maijishan Grottoes were monitored throughout the year. The results indicated that the hygrothermal environment in Cave 101 was in an annual cycle from low temperature and RH to high temperature and RH. Then, a hygrothermal simulation model of the cave was established via the coupled heat and moisture transfer method. In addition, the accuracy of the model was verified by error analysis. Finally, the influences of different factors on the hygrothermal environment in the cave were evaluated by the model. The corridor and door can effectively weaken the influence of climate change on the hygrothermal environment in the cave. With increasing size and decreasing air change per hour, the annual amplitude and diurnal change in temperature and RH in the cave decrease. However, the environment in the cave remains moist in summer. The ventilation dehumidification design could be adopted as a regulation measure. This research provides a quantitative research method for the regulation of the hygrothermal environment and promote the development of preventive environmental protection technology in the Maijishan Grottoes. •Use the coupled heat and moisture transfer method to study the grotto environment.•Present a hygrothermal simulation model of a cave, and verify the accuracy.•Analyze the different factors influencing the hygrothermal environment in the cave.•Provide a quantitative research method for regulating the hygrothermal environment in grottoes.