Lake Nansi consists of four lakes:the Nanyang, Dushan, Zhaoyang and Weishan Lake. It is a lake in the line of the Eastern Route Project (ERP) of the South-to-North Water Diversion Project (NSBD). After the project supply water in 2013, the water quality of Lake Nansi will be affected significantly. Based on the existing theories and methods, a three-dimensional hydraulic control and water quality model of the lake is presented. The model is developed under the Environmental Fluid Dynamics Code (EFDC) model. It was calibrated and verified to hydrodynamic and water quality data, using two sets of observed data from October 1 to December 31, 2006 and January 1 to June 30, 2007, respectively. The observed data including water surface elevation, water temperature, chemical oxygen demand, dissolved oxygen and ammonia nitrogen from five stations is used as forcing for simulations. The model results show that temporal and spatial patterns for hydrodynamic and water quality components are consistent with observed data in the reservoir. Because the direction of the water supply and natural flow is converse, the Lake Nansi is divided into the upper-lake and the lower-lake by Erji dam in the Lake Zhaoyang. Two scenarios of whole supplying water term of the lake were simulated using the model. By the analysis of the variations of the hydraulic control and water quality of the upper-lake and lower-lake, This paper proposed three advices of the ERP operation, which can help the project to give full benefits and improve the water quality.