Abstract: Under coupled influences of human activities and climate change, hydrological alterations are unavoidable and should be addressed in the evaluation of flood risk. In this study, the flood risk in the Pearl River basin, one of the economically developed regions in China, is investigated, based on long term annual maximum series (AMS) from 28 hydrological stations. Results indicate the following: (1) significant hydrological alterations have been identified and alterations of precipitation extreme regimes are one of the pivotal factors triggering hydrological alterations of AMS, as abrupt changes of precipitation extremes occur is similar to that of the AMS in time and space. In the East River basin, however, massive human withdrawal of freshwater, a number of water reservoirs and other hydraulic facilities combine to reduce the flood risk. (2) High flood risk can be found in the upper and middle West River basin and the North River basin with an increasing magnitude of 0–40% and 10–30%, respectively. Besides, frequencies of flood events with return periods of longer than 20 years are found to be significantly decreasing. In the East River basin, however, the frequency of floods with a return period of 20 years is increasing, but the flood volume is greatly decreasing. (3) Higher flood risk due to alterations of hydrological extremes will pose a threat to the existing hydraulic facilities. Furthermore, the higher flood risk in the West River and North River basins will potentially threaten the Pearl River Delta, a densely populated region with highly developed socio-economy. The results of this study will thus be of great value in developing measures for resilience to natural hazards in high development economic and coastal regions.