Nuclear receptors represent a large group of protein transcription factors, that are encoded by the early response genes for a wide range of signals including peptide hormones, growth factors, cytokines, fatty acids, neurotransmitters, stress and physical stimuli. Among the nuclear receptors there is a group of orphan receptors, for which endogenous ligands are not found yet. Orphan receptors, like other members of nuclear receptors superfamily, play an important role in the energy metabolism, growth, proliferation and differentiation of cells, embryogenesis, organogenesis, immunity, circadian rhythms and development of variety diseases. This review is devoted to a group of orphan nuclear receptors NR4A: NR4A1, NR4A2, NR4A3. In the review authors consider structure and mechanisms of working of NR4A receptors as well as their role in maintaining cellular homeostasis and the development of diseases. Particular attention is given to a role of nuclear receptors NR4A in development of malignant neoplasms.