To study the vortex-induced force (VIF) model of a steel box girder with projecting slab, a cable-stayed bridge with a main span of 160 m was taken as the research object in this study. First, a computational fluid dynamics (CFD) numerical simulation method was used to calculate the amplitude characteristics of vortex-induced vibration (VIV) of the steel box girder with projecting slab, and the calculated results were compared with those of wind tunnel tests. Then, the time–history of VIF of the bridge girder was extracted based on the validated numerical simulation results, and a new mathematical model of VIF for the steel box girder with projecting slab was established according to the residual values between the reconstructed and target values. On such a basis, the steady VIV amplitude expression of the bridge girder was deduced according to the principle of the work done by the damping terms in the VIF model. Finally, the performance function of the maximum VIV amplitude was established with six random variables. Furthermore, the failure probability of VIV was calculated by the maximum entropy principle combined with the multiplicative dimensional reduction method, and the sensitivity of each random variable was analyzed as well. The results show that the lock-in region, VIV amplitudes and vibration frequency of the bridge girder calculated from the numerical simulations agree well with those from the wind tunnel tests, and the maximum amplitude occurs at the oncoming wind speed of 7.2 m/s. In addition to the most important fundamental-frequency component, there also exist double- and triple-frequency components in the time–history of VIF of the bridge girder, which implies the VIF exhibits certain nonlinear characteristics. According to the proposed expression of the steady VIV amplitude of the bridge girder, the steady amplitude decreases as the absolute value of parameter [Formula: see text] increases, but it increases with the increase of the parameter [Formula: see text]. The failure probability of VIV of the bridge girder is calculated to be 0.9616 based on the performance function with six random variables. Besides, it is found that the damping ratio [Formula: see text] has great effects on the reliability of VIV, while the vertical bending frequency [Formula: see text] exerts less effects.