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• The driving factors of human appropriation of net primary production (HANPP) were quantitatively assessed. • Eight indicators were introduced to specifically evaluate the impact of human and climate factors on HANPP. • The effect of climate change and human activities to the change of HANPP accounted for 73.2% and 26.8%, respectively. The combined effects of climate change and human activities pose threat to the sustainable development of ecosystems. Human appropriation of net primary production (HANPP) has been extensively used as an important indicator for evaluating the sustainable development of the ecosystem. However, few studies quantitatively assessed the driving factors of HANPP. Based on Moderate-Resolution Imaging Spectroradiometer (MODIS) data, methods of net primary production (NPP) model and regression analysis, the spatial and temporal distribution of HANPP and its driving factors in the Qilian Mountains from 2005 to 2015 were illustrated. The results showed that the HANPP in the Qilian Mountains decreased gradually from both east to west and from south to north, showing a slight upward overall. The regions affected by human activities and climate change accounted for 26.8% and 73.2% respectively. Moreover, there was a significant negative impact between grain yield and HANPP, and a significant positive impact of either the annual sunshine duration, or livestock amount to HANPP. [ABSTRACT FROM AUTHOR]