Objective To investigate the efficacy and safety of triamcinolone acetonide combined with compound betamethasone injection in the treatment of keloid. Methods A total of 108 keloid patients admitted to the Department of Dermatology, Rizhao Yimei Tiancheng Plastic Surgery Hospital from August 2020 to August 2023 were selected as the research subjects. According to the random number table method, they were divided into the control group (n =54) and the observation group (n =54). The control group was treated with conventional triamcinolone acetonide injection, and the observation group was treated with triamcinolone acetonide combined with compound betamethasone injection. The treatment effect, adverse reactions, scar thickness and area, scar score were compared between the two groups. Results The excellent and good rate of treatment in the observation group (92.59%) was higher than that in the control group (74.07%) (P <0.05). The incidence of adverse reactions in the observation group (7.41%) was lower than that in the control group (9.26%) (P <0.05). After treatment, the scar thickness and area in the observation group were better than those in the control group (P <0.05). After treatment, the VSS score of the observation group was lower than that of the control group (P <0.05). Conclusion Triamcinolone acetonide combined with compound betamethasone injection has a good effect in the treatment of keloid, which can effectively reduce the thickness and area of keloid, alleviate scar symptoms, and has a low incidence of adverse reactions, with definite efficacy and safety.