The upper and middle reaches of Heihe River Basin (HRB), which is the second largest inland river basin in the arid area of the northern China, was chosen as study area. Based on monthly normalized difference vegetation index (NDVI) derived from MODIS sensor, monthly temperature and precipitation data observed by meteorological stations, DEM and basic geographical information, the authors analyzed the spatio-temporal change of NDVI and its relationship with climate from 2000 to 2015 using empirical approach. It was found that NDVI in the upper and middle reaches of Heihe River basin increased generally; the increasing rate of NDVI in summer was higher than that in autumn and spring; the area with rapid increasing rate of NDVI was mainly located in the oasis along the Heihe river; the significant decrease of NDVI occurred in the urban areas of Zhangye, Jiuquan and other cities. It is concluded that the correlation of NDVI with precipitation in summer was higher than that with temperature, whereas NDVI in spring and autumn exhibited higher correlation with temperature. NDVI in the grassland, gobi and desert far away from the main river had significant correlation with precipitation in summer, but NDVI in oasis adjacent to the main river did not show the significant correlation with precipitation. The memory effects was also recognized when NDVI responding to precipitation. The general time lag of NDVI variation in summer responding to precipitation was about a month, but it could extend to 2 months. The results are proposed to provide references for regional vegetation restoration and ecosystem management.