Tumour suppressor gene TP53 is a subject of frequent lesions and mutations in a majority of cancer types that is followed by its dysfunction in regulation of cell proliferation, apoptosin and DNA repair. Mutation profile reflects the presence of mutagen-vulnerable sites (including tobacco smoke carcinogens) in its structure. A number of mutations in tobacco smoke-associated cancers are higher than in other types. Particularly, G > T mutation is recognized a signature to benzo(a)pyrene exposure. Further, a mutation profile is dependent on cancer anatomic localization and histological type. There were put forward suggestions concerning estimation of cancer risk and disease prognosis basing of TP53 gene status and expression. The protocols of gene therapy involving TP53 gene are still not satisfactory.