Objective To analyze the effect of local block therapy with fluorouracil injection combined with compound betamethasone injection in the treatment of keloid and its influence on scar aesthetics. Methods A total of 80 keloid patients admitted to Suzhou City Wujiang District Hospital of TCM from January 2023 to December 2024 were selected as the research subjects, and they were divided into the control group and the study group by the random number table method, with 40 patients in each group. The control group was given local block therapy with compound betamethasone injection, and the study group was treated with fluorouracil injection on the basis of the control group. The scar aesthetics, scar length and width, pain and itching degree, and clinical efficacy were compared between the two groups. Results After treatment, the VSS scores of the study group were lower than those of the control group (P <0.05). The scar length and width of the study group after treatment were lower than those of the control group (P <0.05). The scores of itching and pain in the study group after treatment were lower than those in the control group (P <0.05). The total effective rate of treatment in the study group (95.00%) was higher than that in the control group (80.00%) (P <0.05). Conclusion Local block therapy with fluorouracil injection combined with compound betamethasone injection is more effective in the treatment of keloid. It can effectively relieve patients' pain and itching, reduce scar length and width, improve aesthetics, and is conducive to disease prognosis, which is worthy of clinical application.