High mobility group box 1(HMGB1)is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular settings.Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response,immune reactions,cell migration,aging,and cell death.Sepsis is a systemic inflammatory response syndrome(SIRS)that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide,particularly in the aging population.Dysregulated systemic inflammation is a classic characteristic of sepsis,and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes.Here,we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury,the ways by which HMGB1 are released,and the signaling pathways and therapeutics associated with HMGB1.This review highlights recent advances related to HMGB1:the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.