Previous research shows that there is a strong correlation between saltwater intrusion in the Yangtze Estuary and discharge at Datong. In the near future, the discharge of the Yangtze River during dry seasons will decrease due to the construction and operation of large water diversion projects, including the South-to-North Water Transfer Project, which will further exacerbate saltwater intrusion in the estuary. In this paper, a nested 1D fiver network model and a 2D saltwater numerical model are used to associate saltwater intrusion in the Yangtze Estuary with different values of discharge at Datong. It is concluded that 13 000 m3/s is the critical discharge at Datong for preventing saltwater intrusion and controlling the volume of water transferred by the South-to-North Water Transfer Project. Furthermore, based on the analysis of river discharge from Datong to Xuliujing and in consideration of the influence of all of the water diversion projects, operation schemes are proposed for the Eastern Route of the South-to-North Water Transfer Project for different hydrological years.