Cholera was a new type of severe infectious disease which was introduced into China around 1820 in the Qing Dynasty (1644-1911), and the "localization" process was completed rapidly. At present, it is still one of the major threats to the health and safety of human life, and sometimes it causes heavy casualties. In this paper, the spatial-temporal analysis, danger simulation, and boundary detection methods are used to analyze the cholera epidemic in the late Qing Dynasty (1816-1911). The results showed that: 1) because of the strong intervention of cholera, the frequency of the cholera was 77% in the last 100 years in the late Qing Dynasty (1816-1911) which was equivalent to outbreak every 1.3 years, and the contribution rate to the epidemic breadth promotion in the late Qing Dynasty (1816-1911) was about 21.32%, which means that nearly a quarter of the epidemics in the whole Qing Dynasty (1644-1911) were caused by cholera. 2) Cholera had a wide range of suitable habitats in China of the late Qing Dynasty (1816-1911), and the eastern coast was the best suitable habitat. The risk level of cholera epidemic in China was high, and the risk level gradually decreased from east to west, and the risk level in the south was higher than that in the north. There were many factors influencing cholera epidemic, in which the distance from sea level, elevation, sunshine hours, and the maximum temperature were the main factors, and their contribution rates were 29.3%, 22.4%, 16.1% and 7.7%, respectively. This indicates that cholera epidemic was sensitive to geographic factors such as temperature, water source, sunshine and topography. 3) The borderline characteristics of cholera epidemic were obvious in the late Qing Dynasty (1816-1911). The first border was a circular arc with Fengyang as the center and Fengyang-Jiajiang as the radius (the linear distance about 1300 km), which contains about 97.65% of cholera epidemic in this area. The second border was the borderline of cholera high-suitability area, which includes eastern and central provinces of China, such as Anhui, Jiangxi, Hubei , Hunan, and so on. The third border is the enclosed area with the main cholera network as the standard, covering the Bohai Sea, central China, Yangtze River Delta and Pearl River Delta. Almost the entire eastern coastline was covered.