BACKGROUND: Long non-coding RNAs (lncRNAs) participate in spinal cord injury (SCI) development through regulating autophagy and neuronal apoptosis. Previously, MIR155HG was identified as an upregulated lncRNA in rat bladder tissues harvested after SCI operation. Our study aimed to elucidate the function of MIR155HG in SCI. METHODS: Glutamate (Glu)-stimulated primary mouse spinal cord neurons were used as SCI cellular models. Contusion-induced SCI mouse models were established using an improved weightlessness method. Neuronal apoptosis and autophagy affected by MIR155HG or GPNMB silencing were assessed by TUNEL staining, flow cytometry assay, western blotting, and immunofluorescence staining. The binding of miR-7036b-3p on MIR155HG (or GPNMB) was verified by luciferase reporter assay. Histological changes were observed through HE and Masson staining. RESULTS: MIR155HG and GPNMB expression was elevated while miR-7036b-3p expression was reduced in SCI. MIR155HG silencing attenuated the apoptosis in Glu-stimulated neurons and ameliorated glial scar formation and motor function of SCI mice. GPNMB knockdown mitigated apoptosis, enhanced autophagy, activated AMPK phosphorylation, and repressed mTOR phosphorylation. MIR155HG upregulated GPNMB expression by sponging miR-7036b-3p. The autophagy inhibitor 3-MA reversed the above changes caused by GPNMB depletion. CONCLUSION: MIR155HG knockdown alleviated neuronal apoptosis by enhancing autophagy in SCI via miR-7036b-3p/GPNMB axis and AMPK/mTOR pathway.