Background: Background: Acute lung injury (ALI) is one kind of frequently occurred emergency in Intensive Care Unite with a high mortality. The underlying causes are uncontrolled inflammatory reactions and intractable hypoxemia, which are difficult to control and improve. In the past 10 years, gas medical studies have found that both hydrogen molecules and oxygen molecules have protective effects on acute lung injury by improving inflammatory reactions and hypoxia, respectively. Oxygen is an oxidant and hydrogen is an antioxidant. In this study, we investigated the combined effect of above two-gas molecular on lipopolysaccharide (LPS) -induced acute lung injury. Methods: To clarify whether the combination of hydrogen and oxygen could increase or cancel out the protective effect, an ALI mice model induced by intraperitoneal injection of LPS was established, and the degree of lung tissue and mitochondria damage was evaluated based on the pathological sections, inflammatory factors, wet-dry ratio, bronchoalveolar lavage fluid (BALF). Immunohistochemistry, electron microscopy, western blotting and other detection methods also used to evaluate the therapeutic effect on acute lung injury model. Results: We observed that the combined protective effect of hydrogen and oxygen was superior to their respective protective effects, and the specific molecular mechanisms of the two therapies might be different. Conclusion: Hydrogen plays a more important role in the inflammatory and anti-apoptosis mechanisms, while oxygen improves hypoxia of the body, and thus, its molecular mechanism may be closely associated to the hypoxia pathways.