China has planned and built several world-class cascade high dams in Jinsha River, Dadu River, Lancang River, and Yarlung Zangbo River. The complex geological conditions in the reservoir area and numerous large-scale landslide bodies make the potential disaster risk of overflowing and cascade dam failure caused by landslide-generated tsunami under increasing severe situations. However, the study on describing and predicting the complex dynamic processes of generation, propagation, overflowing, wave setup, and the interaction between tsunami and lakeshore has not been systematically carried out. Based on the high-order Boussinesq-type equations, the development of the dynamic system of tsunamis in lakes coupled with the landslide process is realized using the finite volume method in this paper. To verify the accuracy and reliability of the study, the Xiluodu Reservoir is selected as the object to simulate the potential landslide-generated tsunamis. The factors such as the generation and propagation of tsunamis, dam overflowing, and wave setup in the downstream river are quantitatively evaluated and analyzed.The constructed landslide with a total volume of 24×106m3generates a near-field wave amplitude of about 28 m. The maximum wave run-up height is about 95 m, the volume of the dam overflowing water up to 2.13×106m3, and the maximum wave height above the dam crest presents an M-shaped distribution. This LGWs event raises the downstream water level by nearly 40 m. The results show that the risk of landslide-generated tsunamis in the reservoir area in China cannot be ignored. The developed Boussinesq-type equations coupled with the landslide dynamics can simulate the whole process of generation, propagation, runup, and estimating the overflowing water volume of the tsunamis in the lake, laying a foundation for the quantitative risk assessment of tsunamis in lakes of high cascade dams in China.