Spinal cord injury (SCI) was a serious nerve injury, which involves complex genetic changes. This paper was intended to investigate the function and mechanism of differentially expressed genes in SCI. The three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database were used to identify differentially expressed genes (DEGs). We identified the common DEGs in the three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database. Next, a protein-protein interaction (PPI) network of DEGs was constructed. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in immune response, inflammatory response. The expression level of immune-related genes (Arg1, Ccl12, Ccl2, Ifitm2, Ifitm3, and et al.) at different time points of SCI were analyzed in GSE189070 dataset. Next, differentially expressed miRNAs (DE-miRNAs) were identified in SCI compared with normal based on GSE158194 database. DE-miRNA and targeted immune-related genes were predicted by miRwalk, including miR-487b-5p targeted Ifitm3, miR-3072-5p targeted Ccl3, and et al. What’s more, the miR-487b was identified and verified to be down-regulated in Lipopolysaccharide (LPS)-induced BV-2 cell model. Further, the miR-487b inhibited cell inflammation and apoptosis in LPS-induced BV2 cell by targeted Ifitm3. For the first time, our results revealed that miR-487b may play an important regulatory role in SCI by targeted Ifitm3 and provide further evidence for SCI research.