The dynamics model of 2C0 locomotive was set up, wheelset axle-box positioning deviations were analyzed, and the influence of each wheelset axle-box positioning deviation on wheelset lateral displacement and wheelset deflection direction for the same bogie was simulated. Simulation result shows that the axle-box positioning deviation of the first wheelset has greater influence on its lateral displacement, the middle and third wheelset have greater influence on the lateral displacement of the middle wheelset, and the lateral displacement can reach 6.0 mm when the positioning deviation is 2.4 mm. When the deviations exist in any two wheelsets at the same time, the anti-phase positioning deviation has greater influence and more easily results in the partial wear of wheel flange than the same phase positioning deviation, and the lateral displacement can reach 6.5 mm when the combined axle-box positioning deviation is 1.6 mm. The partial wear can be effectively improved by adjusting the positioning deviation.