Introduction: MicroRNAs (miRNAs) are small and non-coding ribonucleic acids that play critical roles in regulation of host genome expression at post-transcriptional level. An individual miRNA is able to down-regulate multiple targeted mRNA transcripts. Therefore, minor changes in a miRNA expression may lead to significant alterations in the expression of different genes. During last two decades, miRNAs have emerged as key regulators of immune cell lineage differentiation, maturation, maintenance of immune homeostasis, and normal function. Multiples sclerosis (MS) is a chronic inflammatory disease that is characterized by infiltration of lymphocytes into the central nervous system (CNS), demyelination and axonal degeneration. Although causes of MS are still unknown, it is widely accepted that novel drug targets need to focus on both decreasing inflammation and promoting CNS repair. Recent researches about MS disease have shown that miRNAs are dysregulated in the immune system and CNS, which shows their role in the MS pathogenesis. Conclusion: Identification of specific expression patterns of miRNA in autoimmune diseases and a further comprehensive understanding of their role in the pathogenesis of different diseases offers promise of not only novel molecular diagnostic markers but also new gene therapy strategies for treating inflammatory autoimmune diseases. In this study, we review the latest findings about miRNA biogenesis and signatures in the CNS and immune cells of MS patients.