In order to propose the measures of adaptation and response to the impact of climate change and human activity on runoff in Lake Honghu basin, to protect the ecological resources of Lake Honghu basin, and to promote its sustainable development, this paper used SWAT model to quantitatively identify the impact of climate change and human activity on runoff in Lake Honghu basin since 1990s. The results show:in recent 20 years, human activity is the main reason for the reduction of runoff in Lake Honghu wetland, its contribution to the reduction of runoff is 63.72%, with a contribution of 36.28% from climate change. The level of influence on runoff change in Lake Honghu Basin varies in different stages, with a higher influence of climate change in 1990s but a higher influence of human activity in 2000s. The measures of water and soil conservation have generated the benefits of runoff adjustment and water conservation in recent 20 years.