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In arid regions, vegetation growth relies on water availability. Climate change can alter water cycling with subsequent effects on vegetation growth. This study examined the effects of projected climate change on vegetation greenness in the middle-reaches region of the Heihe River Basin, the second largest inland basin in China The relationship between the Normalized Difference Vegetation Index (NDVI), an indicator of vegetation greenness derived from remote sensing data, and meteorological factors of precipitation and temperature was simulated using a modified statistical vegetation index simulation model. The model predicted that along with increases in precipitation and temperature, spring and autumn NDVI will rise about 3.8% and 7.9% by the 2050s, respectively. NDVI in summer increases about 3.9%, as increased precipitation may be superior to higher rates of soil water evaporation due to rising temperature. Hydrological processes in the Heihe River Basin are highly influenced by both climate change and human activities. The findings of this study are valuable for the development of water resource management policies that balance the water demands of both human society and the natural ecosystem.