Objective To explore the effect of Kelo-Cote silicone gel combined with fractional CO2 laser on scar improvement in patients with hypertrophic scar after burn. Methods A total of 70 patients with hypertrophic scar after burn treated in Liuyang Jinyang Hospital from September 2023 to July 2024 were selected. According to the random number table method, they were divided into the control group and the observation group, with 35 patients in each group. The control group was treated with fractional CO2 laser, and the observation group was treated with Kelo-Cote silicone gel combined with fractional CO2 laser. The scar severity, scar thickness and hypertrophic scar related factors were compared between the two groups. Results After treatment, the scores of each dimension and the total score of VSS in the two groups were lower than those before treatment, and the scores of each dimension and the total score of VSS in the observation group after treatment were lower than those in the control group (P <0.05). The scar thickness in the observation group after treatment was (2.58±0.41) mm, which was lower than (4.52±0.33) mm in the control group (P <0.05). After treatment, the levels of EGF, TGF-β1 and VEGF in the two groups were lower than those before treatment, and the levels of EGF, TGF-β1 and VEGF in the observation group after treatment were lower than those in the control group (P <0.05). Conclusion For patients with hypertrophic scar after burn, Kelo-Cote silicone gel combined with fractional CO2 laser can reduce the scar severity, improve the scar thickness, and regulate the scar growth factors, which is worthy of clinical application.