Abstract: The Yangtze River mouth is a main headwaters of Shanghai, the water quality of the mouth is affected by both salt water intrusion and pollution from economic development and people's daily life. In recent years, decline in water quality of the mouth has resulted in serious problems of the shortage of water supply in this region. In constructing Three Gorge Water Control Project and in planning the Project of Transporting Water from the Yangtze River to North China, in addition, sea level rise caused by global warming will all affect water quality of the mouth through exacerbated salt water intrusion. Based on the analysis of the affected factors of water quality of the Yangtze River mouth, this paper emphatically studies the integrated impacts of the construction of key water conservancy projects and sea level rise on water quality of Shanghai water intake. The result shows that the construction of Three Gorge Water Control Project and the Project of Transporting Water from the Yangtze River to Northern China as well as future sea level rise will result in the decline of water quality of Shanghai water intake in both South Branch of the Yangtze River and Huangpu River, the obvious effects will appear in October and the dry season of the Yangtze River(from December of this year to March of the next year).