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Introduction. The associative role of the bacterial factor in the development of both primary malignant tumors of the oral mucosa and relapses is being actively discussed today. In the article published earlier, we have already described the possible mechanisms of action of periodontopathogenic microflora and its connection with the development of squamous cell carcinoma of the oral mucosa through cell proliferation, intracellular accumulation of pathogen, DNA replication and affect the signaling pathways of MARK (mitogen-activated protein kinase).Objective – to analyze the impact of periodontal pathogens on the risk of oral squamous cell carcinoma and its recurrence, as well as to evaluate the role of polymerase chain reaction and bacterial culture in the diagnosis of squamous cell carcinoma.Materials and methods. This study included 35 patients with stage Т3–4 squamous cell carcinoma, whose tumor tissue samples were tested for periodontal pathogens using culture and PCR. We analyzed 5 paraffin-embedded and 30 frozen tissue blocks from newly diagnosed (n = 15) and re-treatment (n = 15) patients.Results. We found that PCR was more sensitive than culture for the detection of possible etiological agents and predictors of squamous cell carcinoma (including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) (р