Nb doping is proved to be the most promising way of enhancing the oxidation resistance of TiAl alloys, yet the intrinsic mechanism is still unclear. To understand the effect of Nb doping, a first principles study of several point defects in γ-TiAl during oxidation is performed. Besides the determination of the stable defect structures it is revealed that (1) the formation energy of Nb doping increases with Nb content increasing, at the cost of degradation of the phase stability, which is a hindrance to the oxidation resistance; (2) the abilities of interstitial oxygen and titanium vacancy formation are lowered by Nb addition, thus oxygen diffusion and vacancy formation are reduced correspondingly, which enhances the oxidation resistance of the alloy; (3) the effect of Nb doping on the formation energy of point defect is rather localized, therefore the influence of Nb doping is correlated with its distribution and content in γ-TiAl.