Objective To explore the effect of ablative fractional laser combined with human epidermal growth factor gel on quality of life in patients with facial depressed acne scar. Methods A total of 72 patients with facial depressed acne scar admitted to Xuzhou Central Hospital Afffliated to Southeast University from June 2023 to June 2024 were selected. According to the random number table method, they were divided into the control group and the study group, with 36 patients in each group. The control group was treated with ablative fractional laser, and the study group was treated with ablative fractional laser combined with human epidermal growth factor gel. The clinical efffcacy, quality of life, aesthetic satisfaction and adverse reactions were compared between the two groups. Results The total effective rate of the study group (97.22%) was higher than that of the control group (77.78%) (P<0.05). The scores of quality of life in the study group after treatment were lower than those in the control group (P<0.05). The aesthetic satisfaction rate of the study group (97.22%) was higher than that of the control group (75.00%) (P<0.05). The incidence of adverse reactions in the study group (36.11%) was lower than that in the control group (69.44%) (P<0.05). Conclusion Ablative fractional laser combined with human epidermal growth factor gel exerts favorable clinical efffcacy in the treatment of facial depressed acne scar. It can improve patients' quality of life and aesthetic satisfaction, with high safety.