High mobility group box 1 (HMGB1) is a highly conserved nucleoprotein involving in numerous biological processes, and well known to trigger immune responses as the damage-associated molecular pattern (DAMP) in the extracellular environment. The role of HMGB1 is distinct due to its multiple functions in different subcellular location. In the nucleus, HMGB1 acts as a chaperone to regulate DNA events including DNA replication, repair and nucleosome stability. While in the cytoplasm, it is engaged in regulating autophagy and apoptosis. A great deal of research has explored its function in the pathogenesis of renal diseases. This review mainly focuses on the role of HMGB1 and summarizes the pathway and treatment targeting HMGB1 in the various renal diseases which may open the windows of opportunities for the development of desirable therapeutic ends in these pathological conditions.