How to identify the quantitative effect of climate change and human activities on runoff is a hot topic. As the largest river of Poyang Basin, the hydrological regime changes of Ganjiang River had an effect on water ecosystem health of Lake Poyang Basin. In this paper, the non-parametric Mann-Kendall test was used to analyze the tendency of runoff changes for Ganjiang River in 1955-2010. The impact of climate factors and human activities on runoff was analyzed by statistical methods and IHACRES model. The IHACRES model simulated the streamflow well in Ganjiang River and suitable for subtropical humid monsoon climate zone. The abrupt change of runoff occurred in 1979 and the watershed runoff was divided into two stages, i.e.1955-1979 and 1980-2010. Precipitation is the main factor influencing runoff of the Ganjiang River Basin, while the effect of land cover change on runoff due to human activities is not obvious. The influence of reservoir construction on the seasonal distribution of runoff was significant, with decreases in summer and increases in autumn, especially in 1980-2010. The autumn runoff of about 45% of years in 1980-2010 increased more than 50% compared with that in 1955-1979. In addition, 26% of years showed autumn runoff increase exceeding 100%, with a maximum 320% of autumn runoff increase occurred in 1989.