Monascus purpureus is an important food and drug microbial resource through the production of a variety of secondary metabolites, including monacolin K, a well-recognized cholesterol-lowering agent. However, the high production costs and naturally low contents of monacolin K have restricted its large-scale production. Thus, in this study we sought to improve the production of monacolin K in M. purpureus through overexpression of four genes ( mokC, mokD, mokE, and mokI). Four overexpression strains were successfully constructed by protoplast electric shock conversion, which resulted in a 234.3%, 220.8%, 89.5%, and 10% increase in the yield of monacolin K, respectively. The overexpression strains showed clear changes to the mycelium surface with obvious folds and the spores with depressions, whereas the pBC5 mycelium had a fuller structure with a flatter surface. Further investigation of these strains can provide the theoretical basis and technical support for the development of functional Monascus varieties.