A series of large-scale shaking table tests were conducted to investigate the dynamic response and damage characteristics of the variable-section single pile foundation in liquefiable soil-rock interaction strata under seismic loading. The test results show that the seismic responses of the excess pore pressure ratio under seismic excitations are divided into four stages, among which the difference in the sustained liquefaction stage is the most significant. Pile acceleration amplification is governed by dual coupling effects of soil-pile interaction and structural stiffness. The pile body bending moment distribution features dual-peak characteristics, the largest peak arises at the soil layers interface, while the other peak occurs at the variable-section. Increased seismic excitation accelerates the liquefaction of the saturated sand layer, yet simultaneously slows down the dissipation of the excess pore pressure. As the seismic excitation increases, the acceleration response and displacement response of the pile top are most significant, though maximum bending moment positions remain stable. The stress overrun damage occurs gradually in the variable-section zone under strong earthquakes. Based on the analysis results and the Fourier spectrum modal characteristics of the pile top, the damage mechanism of the pile body is revealed and verified. This study will provide an essential reference for further understanding the seismic response and damage of the variable-section single pile foundation in liquefiable soil-rock interaction strata.