The assessment of the potential degradation risk driven by human activities in ecological red-line regions can provide a scientific basis for the development of differentiated and refined red-line supervision schemes. Taking Anhui Province as an example, based on the InVEST model, the degradation risk of habitat in the red-line region affected by risk sources, such as cropland, construction land, mining area, and traffic trunk was quantitatively analyzed for 2017. The following conclusions were made: the order of habitat degradation risk by human disturbance from high to low was cropland, grassland, wetland, and forest in the whole province and red-line region. The degradation risk of human disturbance in the red-line region was lower than the average level of the whole province. The degradation risk index of the whole province followed the pattern "north high and south low". The high risk areas were concentrated in the suburbs of Hefei, Wuhu-Maanshan, and Huainan-Bengbu cities and the Huainan-Huaibei mining area and its surrounding area, whereas the low risk areas were mainly distributed in the western and southern mountainous areas in Anhui Province, Chaohu Lake, and the lakes along the Yangtze and Huaihe rivers. The red-line patches with high degradation risk were mainly distributed in main canal of the Pihe-Chuhe River and the water source of the Dongda reservoir in the north of Hefei, Qipan Mountain area in Jiao district of Tongling City, the natural shoreline along the Yangtze River in Wuhu-Maanshan cities, the waterbody and natural shoreline along the Huaihe River in Huainan-Bengbu Cities, the Yinghe River and the peripheral wetland in urban areas of Fuyang City and mountain area situated at the juncture of Suzhou and Huaibei cities in the western area of Huangcangyu, and the southeast urban areas in Dangshan County. These key areas are recommended for supervision to prevent ecological risks driven by human activities.