Based on the Hydrodynamic model of MIKE11, the water quality simulation model in the Beijing-Shijiazhuang Section of the Middle Route of South-to-North Water Transfer Project was established. The coefficients calibration and model verification indicated that the established model had a good simulation result. Based on that, models of pollutant migration and diffusion during sudden water pollution accident were established. The model simulated the migration and diffusion of pollutant in the open channel of the Middle Route after dangerous goods transportation accident on the bridge happening. Furthermore, the arrival time and concentration of pollutant in the next turnouts and water discharge gate were also simulated. The obtained results could provide scientific and useful information for emergency plan of sudden water pollution in the Beijing-Shijiazhuang Section of the Middle Route of South-to-North Water Transfer Project.