Objective To investigate the effect of autologous fat gel treatment on serum growth factors and scar improvement in patients with post-burn hypertrophic scar. Methods A total of 64 patients with post-burn hypertrophic scar admitted to the Fourth People's Hospital of Jinan from October 2020 to October 2023 were selected as the research subjects, and they were divided into the control group and the observation group according to different treatment methods, with 32 patients in each group. The control group was treated with hormone drug injection, and the observation group was treated with autologous fat gel. The clinical efficacy, serum growth factors and scar improvement were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.88%, which was higher than 75.00% in the control group (P <0.05). After treatment, the levels of EGF and VEGF in the observation group were lower than those in the control group (P <0.05). After treatment, the scores of appearance, vascular condition, softness and scar thickness in the observation group were lower than those in the control group (P <0.05). Conclusion Autologous fat gel treatment has a definite effect on patients with post-burn hypertrophic scar, which can regulate the levels of serum growth factors and effectively improve scar symptoms. It is worthy of clinical application.