OBJECTIVE: In hypoxia, the most common mechanism of injury is the increase in reactive oxygen species and energy deficiency, which can cause mitochondrial morphology and endogenous apoptosis. This study investigated whether autophagy was activated by a large number of active regulatory processes to adapt cells to hypoxia and help protect against hypoxia. Additionally, the role of lipopolysaccharide (LPS) in this process was assessed. STUDY DESIGN: Mouse-derived dendritic cells were cultured in a hypoxic environment. Cell viability and expression of autophagy-related proteins LC3, Beclin1, and hypoxia-inducible factor–1α (HIF-1α) were detected at different hypoxia time points. Formation of autophagy bodies was observed at different hypoxia times by transmission electron microscopy. RESULTS: After 12 hours of hypoxia the effect of autophagy was obvious, and the formation of autophagosomes increased. The expression of HIF-1α, LC3-II, and Beclin1 was significantly higher than that in the control group, which reached the highest value at 24 hours, whereas the expression in hypoxic 48-hour cells was lower than that in the 24-hour treated group but was still higher than the control group. After LPS was treated, autophagy flux in the hypoxia-LPS group was enhanced as compared with the hypoxia group. CONCLUSION: Hypoxia can induce autophagy in mouse-derived dendritic cells, and simultaneous administration of LPS under the condition of hypoxia can enhance autophagy. The expression of HIF-1α is consistent with the expression of autophagy-related proteins LC3-II and Beclin1, which plays an important role in hypoxia-induced activation of autophagy. © Science Printers and Publishers, Inc.