High entropy alloys (HEAs) have been considered as candidate materials used in the accident-tolerant fuel (ATF) cladding of reactor due to their promising oxidation and corrosion resistance. AlCrFeCuNbx (x = 0.3, 0.5, 0.7, 1) HEAs were designed to improve the accident tolerance of nuclear fuel in this paper. The microstructure, hardness, quasi-critical water corrosion resistance and high temperature water vapor oxidation of the AlCrFeCuNbx HEAs were systematically investigated. The results show that when x is 1.0, the alloy has optimal hardness, water corrosion and high temperature water vapor oxidation resistance. The X-ray diffraction (XRD) analyses showed that the AlCrFeCuNbx HEAs contained a base centered orthorhombic structure and intermetallic compound Cu9Al4. The AlCrFeCuNb HEA had the best performance of 16.7 mg/dm2 weight gain comparable with traditional Zr–1Nb alloy used for nuclear fuel cladding under operating conditions of nuclear power plant water environment of 360 °C and 18.6 MPa for three days keeping, and θ-Al2O3 and NbO formed on the surface of the HEA after water corrosion. The HEA with the same composition had also excellent oxidation resistance (36.77 mg/dm2 weight gain) better than other compositions, which was two orders of magnitude less than that of the Zr–1Nb alloy in the environment of 1200 °C water vapor. Protective α-Al2O3 and CrNbO4 formed on the surface of the AlCrFeCuNb HEA, which prevented further oxidation of the alloy.