The ununiform distribution of the grain size and coarse crystals is easy to be appeared in the high-speed railway axle (HSRA) formed by hot cross wedge rolling (CWR). It seriously reduces the comprehensive mechanical properties of the HSRA. It is vital to numerically predict microstructure evolution, so that the mixed and coarse crystals can be accurately controlled via process parameters optimization. In this study, the microstructure evolution model of the 40CrNiMo steel was developed and implemented into the DEFORM-3D software by programming a user subroutine to simulate hot upsetting. Microstructure of specimens after hot upsetting experiment was investigated to validate the finite element (FE) prediction model of microstructure evolution. The simulation results were close to the experimental results, which verifies that the established microstructure evolution model has a good predictability. The developed microstructure evolution model and the FE prediction system of hot CWR were used to simulate the forming of HSRA. Hot CWR simulations of HSRA was conducted at rolling temperature of 1000 °C and rolling sped of 1.5 r/min with initial grain size of 200um. Numerical prediction of dynamic recrystallization (DRX) volume fraction and average grain size in three segments of CWR, such as wedge entering segment, widening segment and finishing segment, were carried out to study the microstructure evolution of CWR. Results show that the maximum average grain size locates in the heart of hub axle section, which is smaller than grade 5 and above (d≤62.5μm). It indicates that the microstructure of HSRA after CWR meet the requirements of grain structure grade in international standard of EN13261. Effects of rolling temperatures, rolling speeds and initial grain sizes on the microstructure distribution after hot CWR were analyzed using FE simulations for 40CrNiMo steel. The rolling temperature of 1050 °C, rolling speed of 6 r/min and initial average grain size of less than 200μm are suggested to produce HSRA using CWR. Composite manufacturing processes, i.e. free forging plus hot CWR, are suggested to produce HSRA. The material saving as well as improving production productivity simultaneously become a reality. This provides a guiding reference for the actual production of HSRA.