Objective To analyze the efficacy and safety of carbon dioxide fractional laser combined with triamcinolone acetonide in the treatment of hypertrophic scars. Methods A total of 100 patients with hypertrophic scar admitted to our hospital from January 2021 to December 2023 were randomly divided into control group and observation group, with 50 patients in each group. The control group was treated with triamcinolone acetonide, and the observation group was treated with carbon dioxide fractional laser combined with triamcinolone acetonide. The therapeutic effect, scar degree, symptom severity, serum factor level and quality of life were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.00%, which was higher than 82.00% in the control group (P <0.05). The scores of scar softness, thickness, vascular distribution and color in the observation group were lower than those in the control group (P <0.05). The pruritus, pain score and Sa in the observation group were lower than those in the control group (P <0.05). The levels of TGF-β1 and VEGF in the observation group after treatment were lower than those in the control group (P <0.05). The scores of physiological function, social function, mental health and body pain in the observation group were higher than those in the control group, and the differences were statistically significant (P <0.05). Conclusion Triamcinolone acetonide combined with carbon dioxide fractional laser is effective in the treatment of hypertrophic scars, which can effectively improve the degree of scars severity and clinical symptoms, reduce the level of VEGF and TGF-β1, and improve the quality of life of patients. It is worthy of clinical application.