Abstract: Global warming and frequent human activities have widely affected the hydrological cycle processes at regional scales around the world,and a scientific understanding of the runoff evolution driving mechanism is the basis for utilizing water resources scientifically and realizing regional sustainable development.In this study,we analyze the non-consistency of the Heihe River Basin based on the measurement data from 5 hydrological stations and 10 meteorological stations from 1956 to 2020,and compare multiple mutation methods to derive the applicable methods for the basin.Combined with the cumulative slope change rate method and residual analysis method,the interaction between runoff and driving factors is analyzed and quantified.The results show that:(1)The overall hydro-meteorological series of the Heihe River Basin show a significant upward trend with time,among which,the runoff series jumped significantly in 2004.Based on this,the study period was divided into the base period (1956~2004) and the human activity impact period (2004~2020).The precipitation series and temperature series jumped significantly in 2006 and 1996,respectively,and the former has a 10-year lag than the latter.(2)The mutation methods applicable to the long series of meteorological factors in the Black River Basin are Pettitt’s test and ordered clustering;the mutation methods applicable to the hydrological sequences of the stations are the cumulative slope method and the sliding T-test.(3)From the base period to the human activity impact period,the impact of human activities on runoff changed from negative to positive,and the dominant factors affecting runoff were all human activities.The results of the study can provide detailed water resources information and scientific basis for the future development and utilization of water resources in Northwest China.