Abstract⎯This review presents analysis of the literature and our own research with respect to the role of miRNAs in the regulation of activity (expression) of genes controlling cellular homeostasis in human cells when exposed to ionizing radiation. Human cells, on one hand, can have increased resistance to radiation, which hinders the effectiveness of tumor treatment in radiotherapy. On the other hand, increased sensitivity to radiation may be accompanied by the development of several pathologies, including tumorigenesis. This paper examines the role of specific miRNAs in the formation of radioresistance and radiosensitivity of human cells and their impact on the respective target genes. Separate sections are devoted to the role of different miRNAs in radiation therapy of tumors of different localization, as well as their role in the bystander effect. A special section highlights features of gene activity and its regulators, miRNAs, in radiosensitive cells in patients with Down syndrome. The final section provides information about new approaches to change miRNA expression and, accordingly, their target genes by the action of plant and synthetic drugs (crown compounds) which reduce damaging effects of mutagens. It is assumed that antimutagens affecting the expression levels of miRNAs and structural genes may be used to correct the increase and decrease in cellular radioresponse, reducing the risk of development of pathological processes, including tumorigenesis.