Epidemics have always been a great threat to people's health and life security throughout history. To analyze the temporal and spatial variation of epidemic disasters that occurred in the Jiangnan area during 1912-1949, we compiled a list of the epidemic data, and made use of different methods such as historical document review, mathematical statistics and GIS spatial analysis. The results show that: (1)The incidence rate of epidemics was 100% annually and 94.70% quarterly in the time interval. Autumn, summer and spring were usually epidemic seasons, especially in the autumn and summer time. The affected area enlarged year by year, but the fluctuation curve reflected that there were 6 peaks in 38 years. Considering a longer period, i.e. from the Ming Dynasty to the establishment of the People's Republic of China (582 years in total), the return period of epidemic disasters gradually shortened and the number of affected counties increased. It indicates that the epidemic severity in the study period was the highest in the Jiangnan's history. (2)The affected area of epidemics basically spreaded along the Grand Canal and the Nanjing-Shanghai-Hangzhou railway, and the area to their east. Suzhou-Wuxi area and a section of Shanghai adjacent to Suzhou were the hot spots of epidemic disasters, while the mountainous area of Western Zhejiang Province was rarely affected. (3)The general characteristics of epidemic disaster's distributions during 1912-1949 in the Jiangnan area indicate that the hot spots were usually the regions along transportation lines, with a higher population density, or lately suffered severe floods or droughts. Moreover, epidemics spread in plain areas more often and severe than in mountainous areas.