Relevance. The relevance of the treatment of oral mucosa diseases is determined by their prevalence, propensity to progression and difficulties in early diagnosis. The article presents the results of surgical treatment of this category of patients using laser radiation with a wavelength of 1940 nm and determination of gene expression of immunologic factors. Purpose. To increase the efficiency of surgical treatment of oral mucosa hyperkeratosis by using the fiber laser LSP – «IRE-Polus». Materials and methods. Surgical treatment was performed on 30 patients (100%) with clinical diagnosis K13.2 Leukoplakia and other disturbances of oral epithelium, including tongue (25 patients) and L43.0 Lichen ruber planus hypertrophicus (5 patients). All patients were randomly divided into 2 groups: in the 1st group lesions were excised by fiber laser LSP – «IRE-Polus», in the 2nd group excision was performed by scalpel. Sampling for gene expression study of defensin beta 1 and IL-28B genes was performed after surgical intervention in all patients. Statistical analysis was carried out using the Mann–Whitney test. Results. The use of laser alteration leads to a decrease in pain intensity, collateral edema, and the timing of postoperative wound epithelialization. In the expression study of immunologic factors, there was no statistically significant difference in the expression of defensin beta 1 gene in both study groups, while an association was found between a high level of IL-28B gene expression and the development of inflammation when using the traditional method. Conclusion. The use of fiber lasers contributes to the improvement of treatment efficiency in patients with hyperkeratosis of the oral mucosa. When examining patients with hyperkeratosis, a significant 2.2-fold increase in IL-28B gene expression was found in the group of patients where the traditional method of treatment was applied (p < 0.05).