Purpose <p>Spinal cord injury (SCI) is a serious neurological disease, and microRNA (miRNA) plays an important role in various cellular events after SCI. This study aims to explore the expression of miR-582-5p in SCI patients and its regulatory effects on apoptosis, inflammation and oxidative stress during the SCI process.</p> Methods <p>Serum miR-582-5p was detected in 45 patients with limb fractures and 60 patients with SCI by reverse transcription-quantitative PCR (RT-qPCR). The in vitro SCI neuroinflammation model was constructed by inducing BV-2 cells with 100ng/mL lipopolysaccharide (LPS). The SCI model of mice was constructed by Allen’s percussion method. The expression of miR-582-5p, apoptosis, inflammation and oxidative stress factors in in vivo and in vitro models were detected by RT-qPCR, flow cytometry, enzyme-linked immunosorbent assay (ELISA), etc. The motor function of mice in each group was evaluated by the BMS scoring method.</p> Results <p>MiR-582-5p was significantly downregulated in SCI patients, and this result was consistent with that in both the BV-2 cell model and SCI mice model. Functionally, the upregulation of miR-582-5p improved the recovery of motor function in SCI mice and alleviated inflammatory and oxidative stress injuries. In cell experiments, it was confirmed that Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) is one of the target genes of miR-582-5p, and the overexpression of UBR5 can effectively reverse the improvement effect of miR-582-5p in SCI cell models.</p> Conclusions <p>This study reveals the key protective role of miR-582-5p in SCI and its molecular mechanism. miR-582-5p exerts the effects of reducing inflammation and oxidative stress and promoting the recovery of neurological function by targeting and inhibiting the expression of UBR5.</p>