| The "Water diversion project from the Yellow River to Hebei Province" is important for ensuring the water supply in the Xiong’an area, and impacts runoff in a key section of the water diversion project. The objectives of this study were to investigate changes in the runoff regime and identify the driving forces associated with construction of the Yellow River Diversion Project. The results provide a reference for the water resource management that fully accounts for the benefits provided by water resources. A total of 33 hydrological indices and the overall runoff situation of the key section in the Yellow River Estuary, from 1958-2016, were analyzed using the index of hydrologic alteration/range of variability approach (IHA/RVA). The contribution of climate changes and human activities on the variation of runoff was quantified based on six Budyko hypothesis formulas. The study area was the Qucun section, the key section of the Yellow River Diversion Project, and data for calculating the hydrological indices were obtained from the Gaocun hydrologic station, about 7 km from the diversion inflow entrance. The study period (1958-2016) included two stages： TA (1958-2005), before project construction, and TB (2006-2016), after project construction. Annual runoff in the section decreased significantly from TA to TB. After 2006, the overall degree of variation of the runoff regime reached 61.72% and, using a degree of change above 67% as the threshold value, 8 hydrological indices changed substantially. The average contributions of climate change and human activities to variation in runoff were, respectively, 41.79% and 58.21%. Thus, human activities were the primary driving forces affecting runoff in the key section of the Yellow River Diversion Project. Human activities, such as a water conservancy project and soil conservation efforts were major drivers of changes in runoff, consistent with previous research results. To promote the development of water ecology benefits, effective regulation of water and sediment, hydropower and other human activities should be considered.