The invention belongs to the technical field of metal materials and machining and relates to a preparation method of an ultra-fine grain high-entropy alloy. Firstly, smelting is conducted, an FeCoCrNiMn series high-entropy alloy is compounded to be an intermediate alloy composed of pure metal with the purity being higher than 99.5% or alloy elements, a vacuum furnace is adopted for smelting, and the furnace casting temperature is 1550-1600 DEG C; then after cast ingots are subjected to homogenization heat treatment at the temperature of 1000-1350 DEG C, strong deformation asynchronous and synchronous mixed cold rolling treatment is conducted, continuous rolling is conducted through single-pass large percent reduction, the total rolling quantity is no smaller than 85%, and alloy structure nanocrystallization is achieved; and the rolled alloy is subjected to annealing treatment under the temperature of 450-800 DEG C, and the high-entropy alloy of an ultra-fine grain structure is obtained. Compared with the prior art, the preparation method is simple in technique, easy to achieve on a plate rolling production line, high in production efficiency and low in cost; and the size of the prepared ultra-fine grain high-entropy alloy is large, the comprehensive mechanical performance is excellent, and the preparation method can be applied to the fields of engineering machinery, aeronauticsand astronautics, military industry, electronics, instruments and the like.