To elucidate the hot deformation characteristics of TiAl alloys, flow stress prediction, microstructural evolution and deformation mechanisms were investigated in Ti-44Al-5Nb-1Mo-2V-0.2B alloy by isothermal compression tests. A constitutive relationship using the Arrhenius model involving strain compensation and back propagation artificial neural network (BP-ANN) model were developed. A comparison of two models suggested that the BP-ANN model had excellent capabilities and was more accurate in predicting flow stress. Based on the microstructural analysis, bending and elongation of colonies, ? and B2 grains were the main microstructural constituents at low temperature and high strain rate. Dynamic recrystallization (DRX) of ? and dynamic recovery (DRY) of ?/B2 were the main deformation mechanisms. With the increase of temperature and decrease of strain rate, phase transformation played an important role. The flake-like ? precipitates in B2 grains, and a coarsening of ? lamellae via ? lath dissolution during compression were observed. Additionally, the flow softening process commenced with dislocation pile-up and formation of sub-grain boundaries, followed by grain refinement, twins and nano-lamellar nucleation. Continuous DRX and phase transformation promoted the formability of Ti-44Al-5Nb-1Mo-2V-0.2B alloy.