The spatial and temporal distribution of vegetation cover has undergone certain changes in the Tarim River Basin due to the impacts of comprehensive treatment project and recent climate change. Clarifying the relationship between the vegetation cover and the climate change as well as human activities can provide a scientific reference for ecological maintenance and management of Tarim River Basin. Hence, by using trend analysis, R/S analysis, partial correlation analysis and residual analysis, this study analyzed the spatialtemporal changes of NDVI in the growing season and distinguished the range and extent of the impacts of precipitation and temperature changes and human activities on vegetation cover change in the Tarim River Basin from 2000 to 2013. The results showed that:1) The NDVI in the study area has been increasing with an average rate of 0.8%/10 a from 2000 to 2013. The changing rate in plains was significantly higher than that in mountains. The NDVI in growing season in the mountainous areas of Kaidu-Kongque River Basin and parts of the upstream and midstream of the Tarim River Basin presented obvious degradation trend. Meanwhile, NDVI in the downstream of the Tarim River Basin continued going up. 2) The vegetation cover change was mainly affected by climate change in mountain area and the temperature is the main determining factor. The increase of temperature promoted the growth of vegetation. The changes of the vegetation cover in middle-low mountains and the plain area of the mountain pass were the results of the combination of precipitation and temperature, and mainly affected by precipitation. The NDVI showed a positive correlation with precipitation and a negative correlation with temperature. 3) The increasing oasis irrigation area and the comprehensive treatment project for vegetation restoration led to the NDVI increase in the oasis. Human activities are the main driving force for vegetation growth in this area. 4) The ecological brake in the midstream of the Tarim River Basin restored the vegetation in the downstream, but it affected the water usage of the upstream and midstream to some extent. Especially for the midstream, the ecological brake led to the degradation of the vegetation with the rate of 0.1%/ 10 a. The relevant departments should further strengthen the reasonable allocation of the water resources and give full play to the role of the ecological brake for water resources regulation.