ABSTRACT The Kuye River Basin is the main coal-producing area in northwest China, and it is also a typical arid and semi-arid area. Under the combined influence of climate change and human activities, the runoff of the basin decreases noticeably. The Mann–Kendall trend test, the Hurst index, cumulative anomaly, and wavelet analysis were used to analyze the runoff evolution characteristics of the Kuye River, and the contributions of climate change and human activities to the runoff reduction were quantitatively separated by the slope-changing ratio of the cumulative quantity. The results showed that the runoff decreased significantly from 1970 to 2020, and there was an obvious abrupt change in 1996, while the change trends in precipitation and evaporation were not significant. The contributions of climate change and human activities to runoff reduction were 22.71 and 77.29%, respectively, and human activities have become the dominant factor in runoff variations. Coal mining and the implementation of soil and water conservation measures are considered to be the main human activities contributing to the reduction in runoff. In particular, mining activities reduce groundwater recharge to rivers, which provides a profound understanding of the effect of human activities in mining areas on runoff variation.