The metal microstructure during the hot forming process has a significant effect on the mechanical properties of final products. To study the microstructural evolution of the cross wedge rolling (CWR) process, the microstructural model of GH4169 alloy was programmed into the user subroutine of DEFORM-3D by FORTRAN. Then, a coupled thermo-mechanical and microstructural simulation was performed under different conditions of CWR, such as area reduction, rolling temperature, and roll speed. Comparing experimental data with simulation results, the difference in average grain size is from 11.2% to 33.4% so it is verified that the microstructural model of GH4169 alloy is reliable and accurate. The fine grain of about 12-15 μm could be obtained by the CWR process, and the grain distribution is very homogeneous. For the symmetry plane, increasing the area reduction is helpful to refine the grain and the value should be around 61%. Moreover, when the rolling temperature changes from 1000 to 1100℃ and the roll speed from 6 to 10 r·min^-1, the grain size of the rolled piece decreases first and then increases. The temperature may be better to choose the value around 1050℃ and the speed less than 10 r·min^-1.