The effect of V on the high-temperature oxidation performance of austenitic stainless steel has been investigated by the constant-temperature oxidation weight gain approach, while the morphology, composition and elemental distribution of the oxide film are further analyzed by scanning electron microscopy and energy dispersive spectrum, transmission electron microscope and X-ray powder diffractometer as well as X-ray photoelectron spectroscopy, revealing the mechanism of the effect of V on the high-temperature oxidation performance of austenitic stainless steel. As a result, the addition of V has a significant adverse effect on the oxidation resistance of steel. Noteworthy, vanadium pentoxide generated during the oxidation process increases the internal stress of the surface oxide layer, reduces the integrity of the oxide layer and promotes oxygen penetration into the matrix. Simultaneously, the Z-phase formed at the grain boundaries of the matrix inhibits the diffusion of Cr ions, resulting in the inability to form an effective protective layer of Cr2O3 oxidation on the surface.