To study the hot deformation behavior of the Ti–22Al–25Nb alloy, isothermal compression tests were conducted at the temperature range of 930–1080 °C with strain rates of 0.001–1.0 s−1. Both the strain rate and the deformation temperature have a significant influence on the stress–strain behavior of the Ti–22Al–25Nb alloy. A hyperbolic–sine constitutive equation is established to quantitatively demonstrate the relationship between the parameters involved, and the hot deformation activation energy Q is determined as 621 kJ/mol. To optimize the processing window, a hot processing map is established, which is related to the microstructure evolution in hot working. The lamellar globularization as well as the dynamic recrystallization (DRX) would contribute to the stable regions with high power dissipation, while the adiabatic shear bands would lead to unstable regions. Moreover, an Avrami-type kinetics model is applied to examine the evolution of DRX during isothermal deformation process.