Objective To explore the effect of triamcinolone acetonide injection combined with fractional CO2 laser on scar severity in patients with keloid. Methods A total of 90 patients with keloid admitted to the Department of Dermatology, Huaihe Hospital of Henan University from June 2023 to June 2024 were selected as the research subjects. According to the random number table method, they were divided into the reference group and the observation group, with 45 patients in each group. The reference group was treated with triamcinolone acetonide injection alone, and the observation group was treated with triamcinolone acetonide injection combined with fractional CO2 laser on the basis of the reference group's regimen. The scar severity, clinical efficacy, adverse reaction rate and recurrence rate were compared between the two groups. Results After treatment, the scores of thickness, softness, vascular distribution and color in the observation group were lower than those in the reference group (P<0.05). The total effective rate of the observation group (97.78%) was higher than that of the reference group (80.00%) (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). The recurrence rate of the observation group was 2.22%, which was lower than 15.56% of the reference group (P<0.05). Conclusion In the clinical treatment of keloid, the combined regimen of triamcinolone acetonide injection and fractional CO2 laser can effectively improve the texture and height of scar tissue, reduce scar severity, enhance the overall effective rate, and help to reduce the risk of recurrence. This combined therapy has good tolerability, with a relatively low incidence of related adverse reactions.