Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by a diverse array of autoantibody production, complement activation and immune complex deposition, causing tissue and organ damage. Effective medical treatment for SLE is lacking because the etiology and pathogenesis of SLE are incompletely understood. It has been confirmed that cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including SLE. Recently, IL-27 was identified, which belongs to the IL-12 cytokine family. IL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models. In particular, suppressive effects on T(H)17 cells, which are implicated in the pathogenesis of SLE. Moreover, administration of IL-27 or augmentation of IL-27 signaling suppresses some autoimmune diseases, including autoimmune diabetes and murine lupus, suggesting that IL-27 may be therapeutically relevant in SLE. In this article, we discuss the biological features of IL-27 and summarize recent advances on the role of IL-27 in the pathogenesis and treatment of SLE. Even though IL-27 has shown therapeutic potential in SLE, further research, particularly in humans, is needed in order to establish the precise role of IL-27 in SLE.