Objective To explore the effect of autologous fat transplantation combined with carbon dioxide fractional laser in hypertrophic scar after burn and its influence on patients' scar severity. Methods A total of 100 patients with hypertrophic scar after burn admitted to our hospital from May 2023 to May 2025 were selected, and they were divided into the control group (n =50) and the observation group (n =50) by the random number table method. The control group was treated with carbon dioxide fractional laser, and the observation group was treated with autologous fat transplantation on the basis of the control group. The clinical efficacy, scar severity, scar thickness, blood perfusion volume and adverse reaction rate were compared between the two groups. Results The total effective rate of treatment in the observation group (96.00%) was higher than that in the control group (80.00%) (P <0.05). The various mVSS scores, scar thickness and blood perfusion volume of the observation group after treatment were lower than those of the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Autologous fat transplantation combined with carbon dioxide fractional laser has a definite effect in the treatment of hypertrophic scar after burn. It can reduce scar severity, scar thickness and blood perfusion volume, with a low incidence of adverse reactions and good overall effect.