Nitrogen (N) and phosphorus (P) concentrations are the fundamental factors affecting the nutrient status and productivity of lakes, and extrinsic inputs of N and P primarily cause eutrophication of lakes. In this essay, taking Hongze Lake as the study area, a two-dimensional hydrodynamic and water quality mathematical model of Hongze Lake was constructed, and based on calibration and verification of parameters, numerical simulation was performed on the changes in N and P concentrations in this lake after water transfer. The study results exhibited that before and after project construction, the absolute values of rates of changes in the annual average concentrations of ammonia nitrogen (NH4+-N), total phosphorus (TP), total nitrogen (TN), and permanganate index (CODMn) in Hongze Lake were all lower than 20%, which demonstrates marginal changes in the annual average concentrations. By analyzing the seasonal and spatial distribution characteristics of the concentrations of N, P and other pollutants in the lake area before and after the project operation, it is found that the main reasons that affect the water quality change in the lake area after the project operation are the newly added water transfer volume, water transfer location, and water transfer quality.