The objective. The aim of the study was to assess photobiomodulation (PBM) efficacy in management of OM in children during chemotherapy with HD-MTX. Patients and methods. Thirty three children and adolescents with acute lymphoblastic leukemia and non-Hodgkin's lymphoma participated in randomized prospective control study. Ninety three episodes ofHD-MTX chemotherapy were assessed. All patients were administered supportive therapy adopted in the Center. Sixteen children have received PBM of oral mucosa with semiconductor laser with wave length X = 670 ± 0,02 nm in prophylactic (5,16 J/om2) and therapeutic regimens (from 5,16 J/om2 to 21,24 J/om2) during 46 episodes of CT. Results. Oral mucositis was registered in 10 patients (59%) receiving PBM compared to 14 (88 %) patients without this method of prophylactics (p = 0,118), during 30% and 67% of episodes of HD-MTX chemotherapy, respectively (p < 0,001). Frequency of severe oral mucositis in patients receiving PBM was 8% compared to 17% in patients without this method of prophylactics (p = 0,355). The mean for pain assessment according to the Visual Analogue Scale was 0,8 points (95% CI 0-1,8) and 2,3 points (95% CI 1,2-3,4), respectively (p = 0,021), the mean for Lansky score was 91 points (94-99) and 63 points (54-71), respectively (p < 0,001), median of OM duration was 9 days [4-19] and 10 days [2-24], respectively (p = 0,721).Analysis long-term results of treatment of the main disease using general survival rate did not differentiate in groups (p = 0,16). PBM did not have side effects, was well tolerated and easily adopted in the treatment protocols of the Center. The use of PBM decreased the cost of accompanying therapy for the episode of CT by 39%. Conclusion. PBM is safe, effective and available method that can be recommended for management of OM in children and adolescent during HD-MTX chemotherapy.