The aim of the study was to evaluate the diagnostic value of determining the level of hypoxia-inducible factor-1α (HIF-1α) in the gingival fluid in patients with chronic generalized periodontitis (CGP) and exacerbation of inflammatory periodontal diseases in patients with cancer of the oral mucosa (OM). A clinical study was carried out with the participation of 60 patients with CGP (group 1) and 22 patients with cancer of OM (group 2) of the T1—2N0M0 stage, as well as 15 healthy individuals with no revealed periodontal pathology. CGP patients, depending on the depth of periodontal pockets (PC), were divided into two subgroups — with a mild degree (PC depth up to 3.5 mm) and an average degree (PC depth from 4 to 6 mm). Group 2 patients were also divided into two subgroups — with exacerbation of CGP (n=12) and patients with no complications (n=10). The content of HIF-1α in the gingival fluid was determined by enzyme immunoassay. The results of the study made it possible to establish that in patients of group 1, the concentration of HIF-1α in inflammatory exudate increased by 2.4 times (p<0.001) compared with the control group. The concentration of HIF-1α in the contents of periodontal pockets in patients with CGP depended on the severity of the disease: with mild CGP, it did not differ from the control group, and with moderate CGP it was 3.15 times higher (p<0.001). In patients with cancer of OM, the concentration of HIF-1α in the gingival fluid did not depend on the presence of inflammatory periodontal lesions and was determined by a multiple increase in the biomarker level (7.5 times) due to the development of a malignant process in the oral cavity. Therefore, monitoring the concentration of HIF-1α in the gingival fluid is informative in patients with CGP in assessing the severity of periodontal conditions, as well as in differential diagnosis with malignant formations of the oral cavity.