The objective of this study was to assess the effectiveness of photobiomodulation with low-level laser therapy (LLLT) as a preventive and therapeutic procedure for the treatment of oral and oropharyngeal mucositis caused by radio-chemotherapy in patients diagnosed with oral squamous cell carcinoma (SCC). An experimental, prospective, double-blind, randomized controlled study was conducted involving patients diagnosed with oral SCC undergoing oncological treatment. The variables analyzed included grade, appearance, and remission of mucositis. A final sample of 26 patients was included: 11 (42.3%) in the study group and 15 (57.7%) in the control group; their average age was 60.89±9.99years. Statistically significant differences between the groups were observed from week 5 of oncological treatment; 72.7% of the laser group showed normal mucosa (mucositis grade 0), while in the control group, 20.0% showed grade 0 mucositis and 40.0% showed grade 2 mucositis (P<0.01). No statistically significant difference between the groups was found regarding the application or use of medication throughout the study period (P>0.05). The tolerance evaluation did not show any statistically significant difference between the groups regarding the occurrence of side effects or adverse events during the trial (P>0.05). Photobiomodulation with LLLT reduces the incidence and severity of mucositis in patients treated with radiotherapy±chemotherapy.