〔Abstract〕 Objective To investigate the effect of hypoxic preconditioning(HPC) on mitochondrial energy metabolism in mouse hippocampal HT22 cells and its possible mechanism. Methods In this paper, mouse hippocampal nerve cells HT22 were divided into control group, hypoxia group, HPC group, and the levels of adenosine triphosphate(ATP) and reactive oxygen species(ROS) in each group were measured for observing the effect of HPC on cell mitochondrial metabolism. Western blot was used to detect the expression of target of rapamycin(mTOR), phosphorylated mTOR protein and autophagy substrate P62 protein; cellular immunofluorescence was used to detect phosphorylated mTOR, and LysoTrackerTMprobe was used to detect lysosomes. Results Compared with the control group, the ATP level was significantly decreased and the ROS level was increased in the hypoxia group. Exposed to HPC, the ATP level was increased and the ROS level was decreased. Compared with the control group, the expression of phosphorylated mTOR was down-regulated and the expression of autophagy substrate P62 was down-regulated in the HPC group. Conclusion HPC may affect the energy metabolism of HT22 cells through the mTOR/autophagy signaling pathway, thereby exerting a protective effect on the HT22 cells.