Background As a new type of medical gas, hydrogen's selective antioxidant effect is found initially, the recent studies have found that hydrogen could inhibit the excessive oxidative stress, inflammation and exert anti-apoptotic effect to improve sepsis-related organ injury, so as to improve the prognosis of sepsis. Additional, as a signaling molecule, hydrogen also has signaling pathway regulating effect. Objective This review focuses on the signaling pathway regulating effect of hydrogen and its relationship with inflammation, oxidative stress and cellular apoptosis in sepsis. Content This review provided a comprehensive summary of the organ protective mechanism and different signaling pathway regulating effects of hydrogen in sepsis. Trend The hydrogen's signaling patyway regualting effect and its relationship with hydrogen's anti-inflammatory,-oxidative stress and-apoptotic effects in sepsis were summarized to get a comprehensive understanding of the molecular mechanism of hydrogen in the treatment of sepsis.