Although the understanding of sepsis has evolved from"sepsis 1.0"to"sepsis 3.0",and the consensus on clinical management of sepsis has been continuously updated,the incidence rate and mortality of sepsis remain high.Therefore,in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients.This review will focus on the key issues in the basic research of sepsis,and summarize the recent advances and challenges in this field,mainly including genetic polymorphism,microorganisms,high-mobility group box 1(HMGB1),endothelial dysfunction,immunotherapy,and biomarkers,aiming to provide new insights for the diagnosis and treatment of sepsis.