The highway beam bridge was modeled by beam elements, and each car was simulated by multi-body model, vehicles and bridge were taken as an interactive system, and then the vertical vibration equation of the vehicle–beam bridge coupling time-varying system was established. The three-Hermite interpolation function was introduced, the time variability of element interpolation function (TVEIF) which was caused by vehicle-bridge interaction was considered, the contribution of TVEIF to the equation of the bridge-vehicle system was deduced and a program was compiled. The effect of TVEIF on the vertical vibration response of vehicle- beam bridge system was analyzed by a specific example. The results show that the effect of TVEIF on vehicle-bridge coupling vertical vibration of highway beam bridges is significant when the vehicles are crossing the bridge by high speed, so it should be considered during vibration simulation calculation for vehicle-beam bridge coupling system.