Hemorrhagic fever with renal syndrome (HFRS) is an acute natural focal viral disease caused by viruses of the genus hantavirus, characterized by damage to small blood vessels, kidneys, lungs and other organs of a person. MicroRNAs (miRNAs) are 18-22 nucleotide endogenously expressed RNA molecules that inhibit gene expression at the post-transcriptional level by binding to the 3-untranslated region of the target mRNA. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, cell proliferation and differentiation. It has been proven that miRNAs may be involved in the pathogenesis of infectious diseases, including HFRS. Hantavirus infection predominantly affects endothelial cells and causes dysfunction of the endothelium of capillaries and small vessels. It is known that the immune response induced by Hantavirus infection plays an important role in disrupting the endothelial barrier. In a few studies, both in vitro and in vivo, it has been shown that endothelial dysfunction and the immune response after infection with Hantavirus can be partially regulated by miRNAs by acting on certain genes. Most of the miRNAs is expressed within the cells themselves. However, in some biological fluids of the human body, for example, plasma or blood serum, numerous miRNAs, called circulating miRNAs, have been found. Circulating miRNAs can be secreted by cells into human biological fluids as part of extracellular vesicles as exosomes or be part of an RNA-bound protein complex as miRNA-Argonaute 2 (Ago2). These miRNAs are resistant to nucleases, which makes them attractive as potential biomarkers in various human diseases. There is no specific antiviral therapy for HFRS, and the determination of laboratory parameters that are used to diagnose, assess the severity, and predict the course of the disease remains a challenge due to the peculiarities of the pathophysiology and clinical course of the disease. Studying the role of miRNAs in HFRS seems to be expedient for the development of specific and effective therapy, as well as for use as diagnostic and prognostic biomarkers (in relation to circulating miRNAs).