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Karst rocky desertification is a geo-ecological problem in Southwest China. The rocky desertification risk zone delineation could be used as a guide for the regional and hierarchical rocky desertification management and prevention. We chose the middle and lower reaches of the Houzhai underground basin on the karst plateau in Puding County, Guizhou Province, China as the study area and selected land use type, elevation, slope, aspect, lithology and settlement buffer as the main driving factors of the rocky desertification. The potential risk of rocky desertification was quantified with the factor-weights union method and statistical analysis method. Five grades of rocky desertification risk were delineated based on Geographic Information System. The extremely low, low, moderate, high and extremely high rocky desertification risk zones accounted for 5.01%, 44.17%, 33.92%, 15.59% and 1.30%, respectively. As a whole, the rocky desertification risk level was moderate because the area of low and moderate rocky desertification risk zones occupied 78.09% of the study area. However, more than half of the area (about 50.81%) was predicted to have moderate rocky desertification risk and above, indicating that the study area was subject to rocky desertification. Rocky desertification risk was higher in the southeast and lower in the northwest of the study area. Distinct differences in the distribution of rocky desertification risk zones corresponding to different factors have been found.