The present invention provides a radiation resistant high-entropy alloy and a preparation method thereof. A general formula of the radiation resistant high-entropy alloy is TiZrHfVMoTaxNby, where 0.05≤x≤0.25, 0.05≤y≤0.5, and x and y are molar ratios. The preparation method of the radiation resistant high-entropy alloy comprises the following steps: mixing Ti, Zr, Hf, V, Mo, Ta, and Nb in order, and conducting vacuum levitation induction melting or vacuum arc melting, to obtain the radiation resistant high-entropy alloy. The high-entropy alloy in the present invention has an excellent irradiation resistance, and does not suffer radiation hardening damage under simulated helium ion irradiation. When helium bubbles are of same sizes as those of conventional alloy, the bubble density of the high-entropy alloy is far lower than that of the conventional alloy, and the lattice constant thereof decreases abnormally after irradiation.