Objective The aiom of this study was to study the efficacy and safety of berberine as a prophylactic treatment of acute radiation proctitis in postoperative patients with cervical cancer. Methods A total of 120 postoperative patients with cervical cancer were enrolled between July 2016 and October 2019, and randomly divided into a treatment group (berberine 300 mg three times a day, n = 60) and a control group (receiving vitamin C tablets, 100 mg three times a day; n = 60) using the random number table method. All patients received pelvic intensity-modulated radiation therapy (IMRT) and concurrent sensitizing chemotherapy weekly. The difference in the percentage of irradiation volume to the rectum and small intestine as well as the incidence, onset time, severity, and duration of acute radiation proctitis and cystitis during radiotherapy were compared between the two groups. The completion rate, completion time, number of chemotherapy sessions, and quality of life during radiotherapy were also compared. Results There were no statistical differences in age, FIGO stage, pathological type, complications, high-risk factors, and rectum and small intestine irradiation dose distribution (V20, V30, V40, and V50) between the two groups (P > 0.05). No acute radiation proctitis of grade 3 or above occurred in the two groups. There was no significant difference in the incidence of acute radiation cystitis, grade 2 acute radiation proctitis, completion rate of IMRT, and frequency of sensitization chemotherapy between the two groups. After prophylactic treatment with berberine, the incidence of grade 1 acute radiation proctitis, occurrence of grade 1 radiation proctitis, and completion time of radiotherapy in the treatment group were significantly lower than those in the control group (P < 0.05). The SF-36 score of the treatment group after radiotherapy was 67.53 ± 4.21, which was significantly better than that of the control group (64.90 ± 6.32; P < 0.05). The incidence of grade 3-4 neutropenia in the treatment group was 10％ and lower than that in the control group (31.7％, P = 0.003). No adverse reactions related to berberine were observed. Conclusion Prophylactic prescription with oral berberine can reduce the incidence, onset time, and duration of grade 1 acute radiation proctitis, and improve the quality of life of postoperative patients with cervical cancer receiving concurrent chemoradiotherapy.