Objective To analyze the effect of triamcinolone acetonide injection combined with CO? fractional laser in the treatment of keloid. Methods A total of 90 patients with keloid admitted to the Third People's Hospital of Danyang from August 2022 to January 2025 were selected and divided into the reference group and the experimental group by the random number table method, with 45 patients in each group. The reference group was treated with triamcinolone acetonide injection, and the experimental group was treated with triamcinolone acetonide injection combined with CO? fractional laser. The treatment effect, adverse reaction rate and quality of life were compared between the two groups. Results The total effective rate in the experimental group (95.56%) was higher than that in the reference group (82.22%) (P <0.05). There was no significant difference in the incidence of adverse reactions between the experimental group (11.11%) and the reference group (6.67%) (P >0.05). The DLQI score of the two groups after treatment was lower than that before treatment, and that of the experimental group was lower than that of the reference group (P <0.05). Conclusion The application of triamcinolone acetonide injection combined with CO? fractional laser in the treatment of keloid has an ideal effect, which can effectively reduce the incidence of adverse reactions and alleviate the negative impact of skin diseases on patients' quality of life.