Abstract: In order to accurately reveal the impact of high-speed train operation on the vibration response of foundation, the out-of-round wheels and uneven rail surface were introduced to modify the quasi-static moving load. Based on the 2.5D finite element equation of nearly-saturated foundation, a train-track-quasi saturated foundation dynamic analysis model has been established. On this basis, the vibration response of nearly-saturated foundation under different train speeds and loads were analyzed. The results show that both of out-of-round wheels and uneven rail surface have little influence on the time history and peak value of displacement and acceleration at a low speed, whereas the vibration amplitude is significantly increased after the coupling of the two aspects. When the vehicle speed reaches the soil shear wave speed, the influence of out-of-round wheels and uneven rail surface on displacement and acceleration response gradually increases. Compared with the out-of-round wheels, rail surface unevenness has greater influence on nearly-saturated foundation vibration, and it is more sensitive to the change of vehicle speed. The pore water pressure decays rapidly within the range of 0~4 m below the center line of the track bed when the vehicle speed is low, and the pore pressure peak appears at 0.5 m below the track. After the vehicle speed increases, the peak value of pore pressure increases significantly under all kinds of modified loads, and the position of the peak value of pore pressure develops to the deeper part of the foundation under the condition of uneven rail surface and irregular wheel-rail. The vibration response of the nearly-saturated foundation under the irregular wheel-rail coupling condition is obviously greater than that under other load conditions. Therefore, the influence of out-of-round wheels and uneven rail surface should be considered simultaneously in the safety evaluation and foundation vibration response prediction of high-speed railway.