Perfect polyhedral 50-facet Cu2O microcrystals enclosed by high ratio exposed high-index {211}, {522} or {311} facets were successfully synthesized by a facile wet-chemical route under mild temperature and normal pressure. The morphological evolution of 50-facet Cu2O polyhedra was studied carefully and in detail by adjusting reaction parameters such as reaction temperature, reaction time, the concentration and type of alkali metal hydroxides and copper salts, and the amount of the reduction agent glucose. On the basis of these results, a formation mechanism of these polyhedra was tentatively proposed. As compared with Cu2O cubes and octahedra with low-index {100} and {111} facets, respectively, the as-prepared 50-facet Cu2O polyhedra showed higher photocatalytic activities towards the decomposition of the organic dye methyl orange due to more catalytic active sites being held in the high-index facets.