Transmissible spongiform encephalopathies (TSEs), or prion diseases, are irreversible and fatal neurodegenerative disorders associated with the conformational conversion of cellular prion protein (PrP^C), a normal cellular protein, into scrapie prion protein (PrP^Sc), a structural isoform that is infectious and with no effective treatment yet. MicroRNA can regulate cellular protein expression at transcriptional level and may play an critical role in the development process of central nervous system. Recent studies indicate that some specific microRNAs involved in the regulation of innate immune response and inflammation signaling pathways may also be implicated in prion diseases and provide some new insights into the treatment of prion diseases. This review highlights the progress on microRNAs in the occurrence of prion diseases and discusses the leading microRNAs in detail.