Abstract: In order to study the influence of typhoon on the estuary region, a large-scale numerical model covering China’s southeast coast was established, aiming to simulate the process of storm surge generated by the Typhoon In-Fa (No.2106). The comparison with the measured meteorological and water level data shows that the model is stable and reliable and the simulation data is reasonable. Based on this model, the spatial and temporal distribution characteristics of storm surge in the Yangtze Estuary are studied in this paper. The result shows that during typhoon periods, the whole Yangtze Estuary region becomes the storm surge state, and the area with the water increases by more than 0.5 m in height, extending to Lianyungang in the north and Taizhou in the south. The largest storm surges in the river reaches below Nantong are evenly distributed, all about 1.5 m. The variation of storm surges in the upstream area regularly fluctuate with local astronomical tide level. The maximum storm surges occur in the middle of the high tide, the minimum occurs in the middle of the ebb tide, and this regularity gradually disappears in the downstream area. The duration of the storm surges of more than 0.5 m gradually decreases from upstream to downstream.