Background: Episil is a bioadhesive barrier-forming oral liquid gel that can relieve mucositis caused by radiotherapy (RT) and hence relieves pain effectively.The purpose of this trial is to compare the efficacy and safety of Episil in improving acute radiation dermatitis in breast cancer patients. Methods: Key eligibility criteria were as follows: Pathologically confirmed breast cancer; female ≥18 years of age; planning to receive postoperative radiation therapy; surgery with modified radical or breast-conserving surgery; fully healed surgical incision; intact skin in the irradiated area; KPS score ≥80; no severe endocrine or metabolic disease; voluntary participation and signed informed consent; ability to read and understand and good compliance. The primary endpoint was the grading of radiation dermatitis during treatment. Results: A total of 102 patients were included from January 2022 to December 2022. The patients were grouped in a 2:1 ratio by randomized number table method, 67 patients received Episil combined with conventional skin care and 35 patients served as the control group receiving conventional skin care only. Two patients in the Episil group dropped out halfway. According to the RTOG grading, the skin reaction rate and the degree were significantly better in the Episil group than control group (24.62%, 72.31%, 3.08, 0, 0 VS 0, 85.71%, 14.29%, 0, 0, 0) in the 0, 1, 2, 3 and 4 grades respectively (P<0.001). And the pruritus score was significantly lower in the Episil group than in the control group (P<0.05). The results of the EORTC QLQ-C30 Quality of Life Questionnaire showed that the overall health (P<0.05) and overall quality of life (P<0.05) were better in the Episil group than control group after radiotherapy. Relative to the control group, the Episil group produced significantly lower rates of stress, anxiety, and depression (P<0.05) and had less impact on family life and social activities (P<0.05). Most importantly, the Episil group produced fewer pain reactions after the end of radiotherapy. Conclusions: In breast cancer patients receiving radiotherapy, Episil may significantly reduce the grading of acute radiation dermatitis, reduce patient symptoms, and improve patient quality of life. Clinical trial information: ChiCTR2200059646.