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The Laohahe basin is one of the typical semi-arid regions in Northeast China. Quantitatively estimating the contributions of human intervention and climatic variability on runoff changes in this region will help enhance the understanding of local hydrological mechanisms and provide an effective reference for water resources planning and management in other semi-arid regions of the world. The non-parametric Mann–Kendall test was used to analyze the temporal trends of annual precipitation, potential evapotranspiration (PET), and runoff in the whole Laohahe basin and its three sub-basins from 1964 to 2015. The annual runoff showed a decreasing trend in each sub-basin. The change-points of annual runoff detected by Pettitt's test and residual analysis based on double mass curves (RA-DMC) are 1979 and 1998, and the baseline period and change period of each basin are 1964–1979 and 1980–2015. The RA-DMC method and the VIC model were used to quantitatively evaluate the contributions of human intervention and climatic variability to runoff change, which vary in time and space over the past 52 years. The contributions of human intervention to runoff reduction during 1980–2015 was more than 80%. On a multi-decadal temporal scale, human intervention had a stronger impact on runoff during 1980–1989, 2000–2009, and 2010–2015. The influence of human intervention on runoff reduction is gradually increasing in the 21st century. Besides, human intervention has a greater impact in dry years than in wet years. The increase of cropland area leads to a significant increase in irrigation area, which further leads to an increase in the demand for agricultural water, which is also the main reason for the sharp reduction of runoff in the Laohahe basin. [ABSTRACT FROM AUTHOR]