Relative roles of climate change and human activities in desertification are the hotspot of research on desertification dynamic and its driving mechanism. To overcome the shortcomings of existing studies, this paper selected net primary productivity (NPP) as an indicator to analyze desertification dynamic and its impact factors. In addition, the change trends of actual NPP, potential NPP and HNPP (human appropriation of NPP, the difference between potential NPP and actual NPP) were used to analyze the desertification dynamic and calculate the relative roles of climate change, human activities and a combination of the two factors in desertification. In this study, the Moderate Resolution Imaging Spectroradiometer (MODIS)-Normalised Difference Vegetation Index (NDVI) and meteorological data were utilized to drive the Carnegie-Ames-Stanford Approach (CASA) model to calculate the actual NPP from 2001 to 2010 in the Heihe River Basin. Potential NPP was estimated using the Thornthwaite Memorial model. Results showed that 61% of the whole basin area underwent land degradation, of which 90.5% was caused by human activities, 8.6% by climate change, and 0.9% by a combination of the two factors. On the contrary, 1.5% of desertification reversion area was caused by human activities and 90.7% by climate change, the rest 7.8% by a combination of the two factors. Moreover, it was demonstrated that 95.9% of the total actual NPP decrease was induced by human activities, while 69.3% of the total actual NPP increase was caused by climate change. The results revealed that climate change dominated desertification reversion, while human activities dominated desertification expansion. Moreover, the relative roles of both climate change and human activities in desertification possessed great spatial heterogeneity. Additionally, ecological protection policies should be enhanced in the Heihe River Basin to prevent desertification expansion under the condition of climate change.