MicroRNAs and long non-coding RNAs play pivotal roles in the progression and recovery of spinal cord injury (SCI), which is a serious traumatic disease in central nervous system. The purpose of this study was to investigate the expression and clinical value of SNHG3 in SCI patients and explore the regulatory effects of SNHG3 on SCI-induced inflammatory responses in vitro. The relationship between SNHG3 and miR-139-5p was confirmed using a dual-luciferase reporter assay. A SCI cell model was constructed in SH-SY5Y cells using hypoxia treatment. SNHG3 and miR-139-5p expression was analyzed using qRT-PCR. Effects of SNHG3 and miR-139-5p on cell model viability and inflammatory cytokines were evaluated by CCK-8 assay and ELISA kits, respectively. ROC curves based on serum SNHG3 and miR-139-5p were constructed to evaluate their diagnostic performance. In SCI patients, serum SNHG3 was upregulated, but miR-139-5p was downregulated (P<0.05), and a negative correlation between the two ncRNAs was found. Both SNHG3 and miR-139-5p showed relatively high discrimination abilities for the screening of SCI and complete SCI (CSCI) patients. SNHG3 was positively correlated with inflammatory cytokines, and miR-139-5p showed opposite results in SCI patients. By in-vitro analysis, SNHG3 knockdown enhanced cell viability but inhibited inflammation by increasing miR-139-5p. All the data found that serum upregulated SNHG3 and downregulated miR-139-5p served as biomarkers to diagnose SCI and indicate injury severity. The deficiency of SNHG3 alleviated neuronal injury by restraining inflammatory responses through targeting miR-139-5p. Thus, the SNHG3/miR-139-5p axis may provide novel biomarkers and therapeutic targets for SCI.