In recent years of immunology, the understanding of innate immunity has deepened, and the concept of innate immunity has been proposed even in the area of acquired immune subjects. The conventional immunosuppressive treatments have mainly controlled the step of acquired immunity. However, the involvement of innate immunity was clarified for hydroxychloroquine (HCQ), which has been confirmed to be very effective for cutaneous lupus erythematosus (CLE). This review introduces the mechanism of development of CLE from the viewpoint of autoantibodies, cytokines, and innate immunity. Furthermore, the mechanism of HCQ is introduced and discussed.