The invention relates to the field of metal materials and preparation thereof, in particular to an Mo0.5V0.5NbTiZrx high-entropy alloy oriented to nuclear power and a preparation method thereof. The material component of the high-entropy alloy is Mo0.5V0.5NbTiZrx, and the mole ratio of x is within the range of 0-2.0. The preparation method comprises the steps that elementary substances including Mo, V, Nb, Ti and Zr are taken and matched according to the nominal chemical components; during alloy preparation, smelting through a vacuum arc furnace is performed first, the low-melting-point elements are placed on the lower portion of a copper crucible during smelting, the high-melting-point elements are placed on the upper portion of the copper crucible, a working cavity of the vacuum arc furnace is vacuumized, then high-purity argon is introduced, arc striking smelting is performed, and Mo0.5V0.5NbTiZrx high-entropy alloy cast ingots are obtained; and followingly, hot isostatic pressing treatment and homogenizing annealing heat treatment are performed in sequence. The alloy provided by the invention is of a simple single core cube structure, is simple in structure, excellent in mechanical performance and good in high temperature steam corrosion resistance, and has the potential possibility for being applied to nuclear power high-temperature environments. The method provided by theinvention is simple, feasible, and wide in application prospect.