OBJECTIVE: miRNAs are key regulators in multiple sclerosis. To gain a better understanding of the molecular mechanisms of multiple sclerosis, differentially expressed microRNAs (DE-miRNAs) and genes (DEGs) were analyzed. MATERIALS AND METHODS: The miRNA expression profile GSE43590 including 11 samples of peripheral blood T-cells from relapsing-remitting MS patients and 9 normal samples as well as gene expression profile GSE52139 including 8 periplaque samples and 8 normal samples were downloaded from Gene Expression Omnibus. Then, DE-miRNAs and DEGs were identified using limma. Moreover, the target genes of DE-miRNAs were screened. Additionally, the integrated regulatory network of DEGs, DE-miRNAs and targets was constructed using Cytoscape. What's more, the functional modules were also screened using MINE in Cytoscape. Lastly, the functional annotation of genes in modules was conducted using DAVID. RESULTS: A total of 2394 DEGs were screened in 8 periplaque samples. Additionally, 296 DE-miRNAs were identified in the 11 samples of peripheral blood T-cells from relapsing-remitting MS patients. Besides, 6 functional modules (A-F) were screened. Among them, has-miR-197 could target HNF4A. What's more, HNF4A could interact with CYP3A4. Additionally, has-miR-125b could target ID1 and ID3. Besides, ID1 could interact with THBS1. Furthermore, functional enrichment showed that CYP3A4 was significantly related to vitamin metabolic process. For the pathway enrichment, ID1 and ID3 were significantly enriched in TGF-beta signaling pathway. CONCLUSIONS: Some important DE-miRNAs (such as has-miR-197 and has-miR-125b) might be crucial for MS by regulating the expressions of their target genes.