Objective MiRNAs are considered to be crucial for NSCLC’s initiation and development. MiRNAs have been widely identified in NSCLC. However, the role of miR-126 in NSCLC has not been fully explained.Methods miR-126 Expression in NSCLC was evaluated by analyzing the common data sets in Gene Expression Omnibus(GEO) database and reviewing former thesis papers. Three mRNA datasets, GSE18842, GSE19804 and GSE101929, from GEO to indentify the differentially expressed genes (DEG). We prognosed the target genes of hsa-miR-126-5p using TargetScan and analyzed the gene overlap between the target genes of miR-126 and DEG in NSCLC. Subsequently, we analyzed Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We used STRING and Cytoscape to construct a protein-protein interaction (PPI) network, and analyzed the influence of HUB gene on the prognosis of NSCLC.Results A common pattern of mir-126 downregulation in NSCLC was identified in the literature review. A total of 187 DEGs were identified, both NSCLC-related and miR-126-related. Many DEGs are extendedly enriched in cell membranes, signal receptor binding, and biological regulation. Among the 10 main Hub genes analyzed by PPI, 4 HUB genes (NCAP-G,MELK,KIAA0101,TPX2) were obviously related to the poor recuperation of NSCLC patients. When these genes highly expressed, survival rate of NSCLC patients was low. Furthermore, we identified the recessive miR-126-related genes that may be involved in NSCLC, such as TPX2, HMMR, and ANLN through network analysis.Conclusion this study suggests that mir-126 is radical for the biological processing of NSCLC.