Abstract: Lots of large reservoirs have been built in the southwest mountainous areas of China, and the slope of reservoir shore is prone to landslides under complex geological conditions such as rainfall, reservoir water periodic fluctuation and earthquake. If the highway bridge foundation is located in the range of bank slope deformation or instability, huge lateral load may be generated on the bridge pier, thus endangering the foundation structure and the overall safety of the bridge. Taking the slope of Xiaojiang Bridge in Baihetan Reservoir as an example, this study applied GeoStudio to analyse the stability of bridge foundation slope under the combined condition of reservoir water fluctuation, rainfall and earthquake. As to the unstable slope under the combined rainfall condition of reservoir water fluctuation, the numerical method of Tsunami Balls (TB) was used to simulate the landslide dynamic process and evaluate the dynamic impact load of the bridge pier. The results show that the slope stability coefficient decreases due to the reservoir water fluctuation, which is the main factor affecting the slope stability. After seismic load is applied, the slope stability coefficient decreases sharply, while rainfall has limited influence on the stability coefficient. The impact load of the sliding body on the bridge pier increases first and then decreases with time, and the maximum impact load is 13890 kN, which appears after the maximum velocity of the sliding body. It is concluded that the stability of the bridge foundation slope on the bank of reservoir is reduced dramatically under the influence of reservoir water fluctuation, and the failure of the bridge foundation structure may be caused by the instability impact process of TB simulated sliding body. This study provides technical information for the disaster prevention and reduction and safe operation of large reservoir slopes and highway bridges.