The oxidation resistance of Ni-Cr-Al-Fe based powders at 600°C was investigated, and the effects of aluminum content and pre-oxidation treatment on its oxidation resistance behavior were analyzed. The Ni-Cr-Al-Fe based powders were prepared by water atomization. The oxidation kinetics was investigated by conducting the mass increase analyses. The morphology and chemical composition of the oxide films were characterized by FE-SEM (EDS) and XRD, respectively. The oxidation mechanisms of the alloy powders were also discussed by comprehensive analysis of oxidized kinetics and the phase composition of oxide layers. The results indicate that the oxidized kinetic curves of Ni-Cr-Al-Fe based powders at 600°C follow the parabolic rule. The increase of the aluminum content and the pre-oxidation can enhance the oxidation resistance of Ni-Cr-Al-Fe based powders. With the increase of aluminum content, the oxide film changes from a combined structure of Cr2O3 and Al2O3 to single Al2O3 structure, which is beneficial to the increase oxidation resistance of Ni-Cr-Al-Fe based powders. The further oxidation of Ni-Cr-Al-Fe based powders can be effectively controlled after the pre-oxidation treatment.