The quenching process of TC21 titanium alloy forging was simulated by ANSYS finite element analysis software, and the temperature field and the thermal stress field of TC21 titanium alloy forging at different quenching time were obtained, as well as the relationship between the temperature and stress of selected nodes and quenching time. Moreover, the change of microstructure from the forging center to the edge was observed in order to study the effect of cooling rate on the microstructure change. The results show that when the quenching time reaches to 3600 s, the forging surface has cooled to room temperature, while the forging center still maintains a high temperature; the cooling rate increases continually from the forging center to the surface, and the microstructure becomes much finer with the distance from the surface decreasing. At the beginning of quenching, the thermal stress of all parts of the forging rises to the peak rapidly, and then the thermal stress of the surface and the center decrease gradually with the quenching time increasing. The maximum residual stress is only 77 MPa at the end of quenching.