It is of vital significance to study the vegetation cover dynamics and its driving mechanism. Therefore， this research was carried out in Otindag Sandy Land （OSL） area and the individual and interactive effects of seven driving factors on regional vegetation changes were studied using the Geodetector model. The results showed that： （1） The vegetation cover increased in 68.83% area of the OSL from 2000 to 2018， and the significant regions were mainly in the middle and south of the study area （i.e. Abag banner， Xilinhot， Zhenglan banner， Zhengxiangbai Banner and Duolun County）. （2） The relative humidity （RH） and precipitation were the main natural factors affecting the spatial distribution of vegetation cover in the OSL from 2000 to 2018， with explanatory powers of 56.6% and 49.5%， respectively. While the density of total afforestation area and the density of livestock were the main human activities factors， with explanatory powers of 49.1% and 46.4%， respectively. These results indicated that the implementation of ecological engineering had important effects on regional vegetation cover dynamics. （3） The interaction between natural factors and human activities had a stronger impact on vegetation changes than single factors. The interaction between RH and human activities and the interaction between precipitation and the density of livestock were dominated by double synergy. The explanatory power of these interaction impacts were over 60%. However， the interaction between temperature and the density count of large livestock at the end of the year was dominated by non-linear synergy， the explanatory power also reached over 60%.