Objectives: Multiple sclerosis (MS) is the common neurological disorders in young adults, which affects the central nervous system myelin or oligodendrocytes and results in disability. This study aimed to identify the key miRNAs in blood of patients in MS for better understanding the underlying mechanisms of MS. Methods: The publicly available Gene Expression Omnibus data-setsof MS were performed to integrated analysis. miRNA expression and mRNA expression were analyzed in whole blood samples from patients with MS and healthy controls by microarray analysis, Gene Ontology enrichment analyses, Kyoto Encyclopedia of Genes and Genomes pathway analyses, construction of miRNA-mRNA interaction network, and quantitative real-time polymerase reaction. Results: In patients with MS, microarray analysis identified 45 significantly dysregulated miRNAs and 621 significantly dysregulated mRNAs. 1165 negative correlation pairs of miRNA-mRNA were predicted and used to construct the interaction network. hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a occurred as central hubs regulating 87, 38, 34, and 34 genes. Dysregulated mRNAs were significantly enriched in ribosome, tuberculosis, and pathways in cancer. The verification of qRT-PCR displayed that hsa-miR-328-3p was significantly up-regulated in MS and its target genes RAC2 had the down-regulated tendency in MS. hsa-miR-20a-5p had the up-regulated tendency and the corresponding target gene EIF4EBP2 had the down-regulated tendency in MS compared to healthy controls. Discussion: hsa-miR-30a, hsa-miR-93, hsa-miR-20b, and hsa-miR-20a might be the key participant in the pathophysiology of MS involved in signaling pathways including ribosome, tuberculosis, and pathways in cancer.