The purpose of this study was to explore the co-evolution of soil erosion and rocky desertification and their interaction under driving factors and main driving factors in the karst region. In this study, Optimized RUSLE model was used to estimate soil erosion from 2005—2015 in the karst area of Guizhou Province, and the national rocky desertification census database was used to calculate the rocky desertification in the same period, and the Geographic detector was used to explore the interaction between the drivers and the main drivers. The results showed that soil erosion and rocky desertification from 2005 to 2015, karst area in Guizhou Province were mainly moderate and below, soil erosion accounted for more than 58%, and moderate and below rocky desertification accounted for more than 80%; In terms of time, there were similarities and differences in the occurrence time of these two, but during the research period, both of them tended to improve in varying degrees. The incidence of soil erosion in moderate and below rocky desertification was large, and the proportion of above moderate rocky desertification was very small, among which the incidence of soil erosion in no rocky desertification was more than 70%. The explanatory force of the soil erosion driver was the land use > slope > yearly precipitation > elevation > rock exposure rate > vegetation cover > lithology > soil thickness; The explanatory force of the rocky desertification driver was the rock exposure rate > soil thickness > yearly precipitation > elevation > lithology > land use > vegetation cover > slope. The explanatory force of factor combination (interaction) on soil loss and rocky desertification was enhanced compared with the single factor, in which the dominant factor of soil erosion was land use, and the dominant factor of rocky desertification was rock exposure rate; The results showed that the causal relationship between soil erosion and rocky desertification exists and soil erosion develops before rocky desertification, but the simple linear relationship cannot explain the two relationships, but a complex relationship with positive or negative correlation exist in stages. The results can provide theoretical reference for soil erosion and rocky desertification control in karst area.