Abstract <p>8-Oxo-2′-deoxyguanosine (8-oxoG) is one of the most common and biologically significant oxidative lesions of heterocyclic bases in DNA, caused by reactive oxygen and nitrogen species. Its accumulation leads to genomic instability and the development of a wide range of pathologies, including cancer, neurodegenerative, and cardiovascular diseases, making 8-oxoG a universal marker of oxidative stress. The presence of this modification in the DNA template strand promotes base pairing errors during replication, enhancing mutagenesis. Conversely, 8-oxoG is removed by the enzyme 8-oxoguanine DNA glycosylase during base excision repair, the effectiveness of which is determined by the local structural and epigenetic context of DNA. Modern detection methods have shown that 8-oxoG accumulates in GC-rich promoters and regulatory regions, where its presence can influence G-quadruplex formation, cytosine methylation, and gene transcriptional activity. Thus, 8-oxoG is considered not only as a marker of oxidative stress but also as a potential element of epigenetic regulation. This review focuses on current understanding of the mutagenic and regulatory potential of 8-oxoG, as well as the influence of modified units and structural features – from canonical duplexes to non-canonical structures and chromatin – on replication and repair processes, gene expression, and DNA methylation.</p>