It is widely understood that hydrological cycles are complex processes influenced by both climate change and human activities. With global warming, the impacts of climate change and human activities on hydrological processes are of widespread concern and a challenge to researchers and policy markers. The Xinjiang River is located in the Poyang Lake Basin, which is one of the five major rivers in Jiangxi Province. Studies show that in 1990s there was an obvious rising trend in precipitation and a downtrend in evaporation in the Poyang Lake Basin. Meanwhile human activities grew intensely. Thus, the response of hydrological processes to climate change and human activities were investigated in this paper by using the Hydrological Simulation Program Fortran (HSPF), which was calibrated and verified for the baseline period 1960-1990, and then used to reconstruct the natural runoff for the affected period during 1991-2005. The results indicated that: 1) The annual runoff increased by 217.9 and 246.3 mm during 1991-1995 and 1996-2000, respectively, but decreased by 64.1 mm during 2001-2005, as compared with those in the baseline period of 1960-1990. The impact of climate change made about 65.6%-88.0% of the contribution to the changes in the annual runoff, while that of human activities made about 12.0%-34.4% of the contribution to the changes in the annual runoff; 2) Extreme series were affected by human activities. During affected period, the modeled 7-day annual maximum flows and 15-day annual maximum flows were smaller than their observed counterparts; 3) The responses of hydrological processes to climate change and human activities were different. In climate change factors, the increase of precipitation played a significant role in the increase of runoff in 1990s, while the decrease of evaporation played minor role. Human activities such as tree planting, urbanization and reservoir construction were the secondary factors that can influence annual runoff. In this study, we found that reforesting can increase runoff while urbanization and the reservoir construction will cause runoff decrease. It can be predicted that with the development of the Xinjiang River Basin, human activities will exert more influence on river discharge of the basin.