After the excavation of underground masonry heritage sites, fluctuations in environmental conditions, such as temperature and water content, are associated with many diseases, including shrinkage and cracking, salting out and microbial growth, etc. These increase the risk of accelerated deterioration of underground masonry heritage sites and are not conducive to the effective conservation of cultural relic value. We took the Shangfang Eastern Wu Tomb in Nanjing as the research object in order to clarify the correlation between the dependent environment and disease characteristics of semi-underground masonry building sites. We carried out an on-site survey, mapping and disease investigation, and also conducted indoor and outdoor environmental monitoring of the tomb for one year using monitoring facilities such as a weather station and temperature and humidity recorders. Parameters (temperature and relative humidity) outside, inside the protective shelter and within each of the burial chambers were compared, and correlations between different diseases and their dependent environments were made. These clearly defined the corresponding risks of deterioration in different areas of the burial chamber and could provide a reliable basis for the preventive conservation of semi-underground masonry building sites such as the Shangfang Eastern Wu Tomb and other sites as well.