High Mobility Group Box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its pro-inflammatory and immunostimulatory properties. Elevated expression of HMGB1 was found in the sera of patients and mice with systemic lupus erythematosus (SLE). In addition, it has been shown that HMGB1 may act as a proinflammatory mediator in antibody-induced kidney damage in SLE. All theses findings suggest that HMGB1 have important biological effects in autoimmunity that might be a promising therapeutic target for SLE. In this review, we will briefly discuss the biological features of HMGB1 and summarize recent advances on the role of HMGB1 in the pathogenesis and treatment of SLE.