Micro- and nanoparticles with high-index facets may exhibit higher chemical activities that are of great importance in practical applications. Cuprite is a potential alternative to expensive noble metals as the catalyst for CO oxidation at moderate temperatures. We report here a solution based approach to the preparation of unusual polyhedral 50-facet Cu2O microcrystals with a morphological yield higher than 70%. It has been revealed that the concentration of OH- and the volume ratio of polar organic solvent to water in the mixed solvent play crucial roles in controlling the morphology of Cu2O microcrystals. The formation of the 50 facets could be geometrically viewed as the truncation of all the 24 vertices of a small rhombicuboctahedron having 26 facets. When growing from solutions, however, the anisotropic growth rates along the 100 , 110 , and 111 directions might be responsible for the formation of this morphology. The Miller index of the 24 nearly isosceles trapezoids could be assigned to {311} planes based on geometrical analysis and was verified by simulated models using the WinXmorph software and supported by TEM and ED observations. Compared with other polyhedral Cu2O microcrystals, the as-prepared microcrystals showed a higher specific catalytic rate toward CO oxidation.