Qilian Mountain National Park is located in the north piedmont of Qilian Mountains at the intersection of Qinghai-Tibet, Mongolian-Xinjiang and Loess. As one of the national park system pilots, Qilian Mountain National park is an important ecological function area, a water retention area and a priority area for biodiversity conservation in China, and its ecological functions cannot be ignored. Based on the Normalized Difference Vegetation Index (NDVI) and Net Primary Productivity (NPP) of Qilian Mountain National Park from 2000-2019, combined with temperature, precipitation, land use, mineral extraction and tourism development data, we used the Theil-Sen slope estimation, Mann-Kendall test, land transfer matrix and multivariate residual analysis methods to analyze the spatial and temporal distribution characteristics of vegetation, change trend characteristics and its response to climate change and human activities. The results showed that (1) NDVI and NPP in Qilian Mountain National Park from 2000 to 2019 showed a spatial pattern of high in the southeast and low in the northwest, decreasing from southeast to northwest. Temporally, they showed an increasing trend, with an increase rate of 0.0053/a and 0.0014/a, respectively. (2) The improved, decreased and stable areas of NPP in Qilian Mountain National Park accounted for 87.29%, 0.40% and 12.30% of the total area, respectively. Decreased areas are scattered throughout the national park, with the most concentrated distribution at the intersection of Zoulang South Mountains and Lenglongling, near the border edge of Gansu and Qinghai provinces. The improved areas are widely distributed, especially the most obvious in the eastern part of the national park. (3) The NDVI of Qilian Mountain National Park shows a significant positive correlation with temperature in about 40.18% of the area, and a positive correlation with precipitation in about 25.70% of the area, the increase in temperature and precipitation promotes the growth of vegetation in the national park, and a suitable combination of hydrothermal conditions is more favorable to the growth of vegetation.(4) The impact of human activities on vegetation changes was two-sided:Approximately 28.91% of mining, tourism and hydroelectric power stations in the national park still had poor vegetation growth after rectification and regulation, and the ecological environment has not recovered significantly; The cropland to forest and grassland conversion projects and ecological forest projects have been effective, the area of forest and grassland has increased, in the past three years.(5) Most of the vegetation cover changes in Qilian Mountain National Park were caused by a combination of climate change and human activity.