The piles of bridge built on soft clay foundation produce additional settlement due to cyclic loading of moving trains, which affects the operation safety of the train. Dynamic model of vehicle-bridge system and settlement model of pile foundation-soil system are established. Reaction force induced by the moving vehicle is got from dynamic model, firstly, which is taken as excavation of settlement model to study the train-induced cumulative settlement. Then, the additional track irregularity induced by settlement pier is overlaid to original track irregularity, and consider the influence of the vertical centrifugal force induced by settlement pier, which influences on running safety of train is studied by dynamic model. Calculation is performed with German ICE3 train running on the 32 m three-span simple-supported beam. The calculated results show that most cumulative settlement occurs in the range of 10 m below the pile bottom. Relative camber of the bridge induced by adjacent pile settlement is more dangerous to running safety of the train, because the train bears vertical centrifugal force in the direction opposite to the settlement direction, when it runs on the bridges with camber.