The hot deformation behaviors of a Ti46Al2Cr2Nb alloy were investigated at strain rates of 0.001–0.1 s−1 and temperatures of 910–1060 °C. Under given deformation conditions, the activation energy of the TiAl alloy could be estimated as 319 kJ/mol. The experimental results were predicted by different predictive models including three constitutive models and three data-driven models. The most accurate data-driven model and constitutive model were an artificial neural network (ANN) and an Arrhenius type strain-compensated Sellars (SCS) model, respectively. In addition, the generalization capability of ANN model and SCS model was examined under different deformation conditions. Under known deformation conditions, the ANN model could accurately predict the flow stress of TiAl alloys at interpolated and extrapolated strains with a coefficient of determination (R2) greater than 0.98, while the R2 value of the SCS model was smaller than 0.5 at extrapolated strains. However, both ANN and SCS models performed poorly under new deformation conditions. A hybrid model based on the SCS model and ANN predictions was shown to have a wider generalization capability. The present work provides a comprehensive study on how to choose a predictive model for the flow stress of TiAl alloys under different conditions.