The invention relates to a preparation method of a large-size thin-wall foam sandwich structure. The preparation method comprises the following steps: (1) laying a prepreg on the outer surface of a die, and solidifying for forming inner skin units, wherein the inner skin units are of cavity structures with closed sections; (2) connecting the multiple inner skin units together in sequence along the axis direction of a cavity by an edge overlapping and adhering mode to form an inner skin; (3) adhering a foam plate to the outer surface of the inner skin; (4) culling foam from parts, in which reinforcement blocks are pre-buried, on the outer surface of the inner skin, and adhering the reinforcement blocks to the parts; and (5) laying the prepreg on the outer surface of the foam plate, then laying an auxiliary material, and performing vacuumizing and solidifying to obtain the whole outer skin. The large-size thin-wall foam sandwich structure prepared by the technical method has the advantages of light weight, excellent heat insulation performance, high rigidity and the like; furthermore, the die investment cost is low; the technical process is simple; the preparation method is convenient to operate and the large-size thin-wall foam sandwich structure is extremely high in practicability.