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• A comprehensive framework for quantifying the climatic and anthropogenic influences on river hydrological health is proposed. • Human activities significantly aggravate the degradation of river hydrological health for the studied catchment. • Widespread artificial water withdrawal and reservoir operation are the two crucial human activities. • Adequate rainfall maintains the river hydrological health at a good status in the 1990 s. Climate change and human activities have together altered the river hydrological regime and consequently threatened the health of river ecosystems. Quantifying the impact of climate change and human activities on river hydrological health regimes is essential for water resource management and river ecology protection. Although previous studies have analysed the hydrologic alterations using some indicators, separating effects of climate change and human activities on river hydrological health is needed for developing adaptive measures to protect the ecosystem of river basins. In this study, a comprehensive assessment framework for quantifying climatic and anthropogenic influences on river hydrological health variation was proposed. The framework consists of the following steps: (1) the reconstruction of natural river streamflow using the variable infiltration capacity (VIC) hydrological model, (2) calculation of river hydrological health through the ecological flow threshold method, and (3) quantification of the impacts of climate change and human activities on river hydrological health using the 'observed–simulated' comparison approach. The semi-arid Laohahe Basin in northern China, which consists of three human-influenced catchments (Taipingzhuang, Chifeng, and Xinglongpo) and one natural catchment (Xiquan), was selected as the case study area. The case study demonstrated that the proposed procedure is efficient in quantifying climatic and anthropogenic influences on river hydrological health. The results revealed that the hydrological health level has significantly declined in the three human-influenced catchments for the human-influenced period (1980–2016), particularly in the 2000 s and 2010 s, where it degraded much more severely. Whereas, the relatively adequate rainfall in the 1990 s maintained the river hydrological health at a good status. The quantitative evaluation showed that human activities were the main driving factors for the hydrological health degradation during the whole human-influenced period, with contributions of 80.8%, 91.9%, and 86.0% for the Taipingzhuang, Chifeng, and Xinglongpo catchments, respectively. Widespread artificial water withdrawal and reservoir operation were the two crucial human activities that caused the degradation of river hydrological health for the studied catchment. The proposed procedure and findings of this study not only help in deeper understanding of the evolutionary characteristics and driving mechanisms of river hydrological health in a changing environment in general, but also provide scientific basis for local water resources management and river ecosystems protection. [ABSTRACT FROM AUTHOR]