Abstract: Objective To study the curative effect of transdermal fentanyl in patients with esophageal cancer who had pain due to radiotherapy-induced acute esophageal mucositis. Methods Thirty patients with pathology-confirmed esophageal cancer, who had moderate and severe pain due to radiotherapy-induced acute esophageal mucositis, were divided into treatment group and control group (15 each group). The patients in treatment group received chemotherapy plus transdermal fentanyl therapy and those in control group received only chemotherapy. Their pain, quality of life, and adverse reactions were observed during and after treatment. Results The effective pain relief rate was 86.67% in treatment group and 20.00% in control group. The incidence of adverse reactions was lower in treatment group than control group. The patients in treatment group could tolerate the treatment. Conclusion Transdermal fentanyl is effective on radiotherapy-induced moderate and severe pain due to esophageal mucositis in patients with esophageal cancer with few adverse reactions and a strong analgesic effect, and is thus beneficial to the successful radiotherapy.