In view of the vibration response and fatigue life of the heavy haul railway tunnel with base voids, a three-dimensional model of train-tunnel-rock is established. Through the secondary development, the fitted train vibration load is directly applied to the track to simulate the driving process of the train, and the analysis of the vibration response characteristics of the heavy haul train to the base structure during the operation process is realized. The vertical displacement, acceleration and maximum tensile and compressive stress of the inverted arch when the 30T axle-loaded train passes through the tunnel with different base voids are obtained. Combined with the life prediction theory of concrete, the fatigue life prediction value of the inverted arch under different base voids is calculated. And according to the predicted life, the reliability of the arch is divided into four levels: safety, vigilance, danger and very dangerous. The conclusion has certain value for the evaluation, treatment and fatigue life analysis for the basement of heavy haul railway with base voids.