Interleukin-21(IL-21) is the most recently discovered member of the type-I cytokine family. Structurally, IL-21 shows homology to IL-2, 4, and 15 proteins. It has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Many previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. In addition, recent work has explored the role of IL-21 in systemic lupus erythematosus (SLE). Elevated expression of IL-21 was found in the sera of patients and mice with SLE. Moreover, association of IL-21 and IL-21R polymorphisms with susceptibility to SLE have been reported. All these findings suggest that IL-21 may have promise as a potential therapeutic target for SLE. In this review, we will discuss the biological features of IL-21, the IL-21 signaling and its potential role in SLE.