Abstract: Scenario simulation analysis of abrupt water pollution is important for risk prevention and control and emergency response. Based on the analysis of risky substance leakage scenarios of chemical enterprises, MIKE21, a two-dimensional hydrodynamic-water quality coupling model, was used to simulate the abrupt water pollution accident in the Tongling section of the mainstream of the Yangtze River. The model verification showed the constructed hydrodynamic model could meet the accuracy requirements. The simulation results of three different leakage scenarios for one chemical company's storage tank showed that: in the same hydrological period, the pollution degree and time of risky substances to downstream sensitive receptors were mainly related to the total amount of leakage, and it had the most serious impact on downstream sensitive receptors when the storage tank was leaked entirely, and the maximum pollution peak was 2~3 orders of magnitude higher than 20% and 100% pipe diameter leakage. In different hydrological periods, risk substances took the shortest time to get to downstream sensitive receptors in the wet period, and it took 75 min for the risky material to reach the water intake of the Third Water Plant when the storage tank was leaked completely; but it took 103 min and 111 min during the normal and dry periods, respectively, and the impact time was longer and the concentration was higher. And there were two pollution peaks successively at the water intake of the downstream plant and the outbound section of the city in the normal and dry periods.