Abstract— <p>S-nitrosoglutathione (GSNO) is an endogenous donor of nitric oxide (NO), which, at the same time, can act both as a signaling molecule and as a toxic agent, forming reactive nitrogen species. The purpose of this work was to study the mechanism of NO involvement in regulation of the function of erythroid nuclear factor 2 (Nrf2), which is a redox-sensitive transcription factor. It was shown that when GSNO was exposed to human hepatocellular carcinoma cells (HepG2), the level of intracellular NO increased dose-dependently during incubation for 24 and 72 hours. The maximum increase in NO level at 100 μM concentration led to a decrease in the amount of non-protein SH groups, to maximum increase in 3-nitrotyrosine and bityrosine levels, which contributed to the decline of cell viability. The NO donor, S-nitrosoglutathione, activated Nrf2 during the 24-h exposure, most likely due to nitrosylation of the Keap1 protein; the 72-h exposure not only activated Nrf2, but also led to an increase in its amount. This process was carried out through the NO-cGMP signaling pathway. The activation of Nrf2 is the key factor in protecting cells from the toxic effects of nitrosative stress products.</p>