The sensitivity assessment of land desertification is one of important contents of monitoring, preventing and controlling desertification. This paper took the arid region of Northwest China as the study area. Based on the RS and spatial analysis technology of GIS, we built a comprehensive index system of desertification sensitivity for evaluation on "soil-terrain-hydrology-climate-vegetation". The spatial distance model (SDM) was used to calculate the desertification sensitivity index (DSI). Then, spatiotemporal change of land desertification sensitivity in the study area covering 2000, 2005, 2010 and 2017 was quantitatively assessed. On this basis, the main driving factors were analyzed by using the geographic detector. The results showed that: (1) terrain, soil, climate, vegetation and hydrology affected each other, which were the basic conditions for the distribution and changes of sensitivity to desertification in the study area. (2) On the whole, the desertification sensitivity showed a distribution pattern of low around and high inside. The low sensitivity regions were mainly distributed in the five major mountain ranges (i.e. Altai Mountains, Tianshan Mountains, Kunlun Mountains, Altun Mountains and Qilian Mountains), and Junggar Basin, Tarim Basin and Inner Mongolian Plateau belonged to the high sensitivity regions, including the back-land of Taklamakan Desert, Badain Jaran Desert and Tengger Desert. Besides, the spatial distribution of desertification sensitivity had obvious regionality, and high and low sensitivity regions had clear boundary and concentrated distribution. (3) In terms of spatiotemporal evolution, changes of desertification sensitivity since 2000 was mainly stable type, and the overall sensitivity showed a slow decrease trend, indicating that the potential desertification regions decreased year by year and some achievements had been made in the control of regional desertification. (4) Among the driving factors affecting study area, soil and climate played a direct role, which were the most important influencing factors, and vegetation was the most active and basic factor that changed desertification sensitivity. In addition, topography and hydrology played a role in restricting the changes of desertification sensitivity, while socio-economic factors were affecting the regional desertification sensitivity, and their effects were gradually strengthened. In general, desertification has been effectively controlled in the study area, and positive results have been achieved in desertification control. However, against the backdrop of intensified global climate change and new normal of socio-economic development, the monitoring, assessment and control of desertification in China still have a long way to go.