In this work, the hot rolling process of Ti-44Al-5Nb-1Mo-2V-0.2B thick plates was simulated using the Marc finite element simulation software. A three-dimensional thermomechanical coupled finite element model was established to analyze the temperature, equivalent stress, and equivalent strain at various positions of the TiAl alloy during rolling, with a particular focus on the distribution characteristics of equivalent plastic strain along the thickness direction of the thick plates. Subsequently, the hot-pack rolling of the Ti-44Al-5Nb-1Mo-2V-0.2B alloy was performed based on the simulation results. The investigation encompassed the evolution of the microstructure along the thickness direction of the TiAl alloy and the impact of the primary rolling on its thermal deformation capacity. The obtained results reveal that the microstructure of the primary rolled sheets predominantly comprises a small amount of residual laminae and fine mixed phases consisting of B2, γ, and α2. The equivalent plastic strain increases gradually from the edge to the center of the sheets, leading to the significant softening of the microstructure in the center of the sheets. This effect induces a corresponding decrease in the residual laminae content from the edge to the center. Consequently, the preparation process for the Ti-44Al-5Nb-1Mo-2V-0.2B alloy was determined based on the influence of the hot rolling process on the microstructure. During the rolling process, as the sheet thickness decreases, it is advisable to appropriately increase the number of reheating cycles or extend the reheating time and simultaneously reduce the amount of rolling deformation. This approach helps minimize the temperature and strain distribution gradient from the core to the edge of the sheets. Additionally, in the later stages of the rolling process, further refinement of the microstructure can be achieved by raising the rolling temperature.