The health of a river ecosystem is the foundation of the sustainable development of a basin, while the natural variability of the hydrological regime is a key factor for maintaining and protecting the ecological health of a river. Therefore, variation attribution of the hydrological regime in the changing environment becomes more important. In this study, the Laohahe basin was selected as a case study area and its hydro-meteorological data during 1964-2016 were collected to achieve the study aim. Firstly, the study period was divided according to the trend and change points test results of Mann-Kendall, Pettitt and precipitation-streamflow double cumulative curve method. Then, the natural streamflow series was reconstructed using the Variable Infiltration Capacity (VIC) model. After that, the principal component analysis (PCA) was used to select the most ecologically relevant hydrological indicators (ERHIs). Then the degree of the change of the hydrological indicators was evaluated by the range of variability approach. Finally, the 'simulated-observed' comparison method was adapted to quantify the impacts of climate change and human activities on the variations of streamflow and ERHIs. The results showed that the annual streamflow series of the basin had a significant downward trend (α < 0.05) and its change points appeared in 1979 and 1999, respectively. Then the whole study period could be divided into base period, changed period Ⅰ and Ⅱ based on the above two change points. Then, 7 ERHIs were selected, including February flow, June flow, annual maximum 7-day flow, Julian day of each annual 1-day minimum, number of low pulse each year, mean duration of high pulse within each year, and rise rate. The 6 ERHIs, February flow, June flow, annual maximum 7-day flow, number of low pulse each year, mean duration of high pulse within each year, and rise rate, had a downward trend. While the Julian day of each annual 1-day minimum showed a slight upward trend. Also, the comprehensive degree of change of the 7 ERHIs are 0.45 and 0.74, respectively in the changed period Ⅰ and II. The quantitative attribution results showed that human activities were the dominant factors to cause the changes of ERHIs, and their impacts on hydrological regime during the changed period II were more severe than those during the changed period Ⅰ. This study proposed a comprehensive method for the optimal selection of the most ecologically relevant hydrological indicators and their evolutionary attributions. Then the method was used to reveal the dominant driving factors of the ERHIs change at different periods. These methods and findings will provide a scientific basis for water resource management under changing environment.