Objective To investigate the clinical effect of local injection of triamcinolone acetonide combined with fluorouracil in the treatment of keloid. Methods A total of 40 patients with keloid admitted to our hospital from February 2022 to February 2023 were selected as the research objects. They were divided into conventional group and experimental group by random number table method, with 20 patients in each group. The conventional group was treated with local injection of triamcinolone acetonide, and the experimental group was treated with local injection of triamcinolone acetonide combined with fluorouracil. The clinical efficacy, scar condition, skin pigmentation rate and incidence of adverse reactions were compared between the two groups. Results The total effective rate and Vancouver Scar Scale score in the experimental group were better than those in the conventional group (P <0.05). After treatment, the skin pigmentation rate of the experimental group was lower than that of the conventional group (P <0.05). The incidence of adverse reactions in the experimental group was lower than that in the conventional group (P <0.05). Conclusion Local injection of triamcinolone acetonide combined with fluorouracil injection can improve the clinical efficacy for patients with keloid, effectively improve the scar condition and skin pigmentation rate, and reduce the incidence of adverse reactions, which is worthy of application.