In designing the structures of railway rolling stocks, deterministic methods associated with the concept of a safety factor have been traditionally used. The deterministic approaches based on the mean values of applied loads and material properties have been used as safety verification for the design of the car body structures. The uncertainties in the applied loading for the high speed train and the strength of new materials in the structure require the application of probabilistic approaches to ensure fatigue safety in the desired system. Pressure loadings acting on the car body when the train passes through tunnels show reflected pressure waves for high-speed trains and they may cause a fatigue failure in vehicle bodies. In this paper, it is proposed that a fatigue design and assessment method based on a structural reliability that deals with the loading of pressure variations on a railway vehicle reflected in tunnels and the strength variations of material. Equation for the fatigue reliability index has been formulated to calculate the reliability assessment of a vehicle body under fluctuating pressure loadings in a tunnel. Considered in this formulation are the pressure distribution characteristics, the fatigue strength distribution characteristics, and the concept of stress-transfer functions due to the pressure loading.