Objective To analyze the effect of 1565 nm non-ablative fractional laser combined with salicylic acid on skin barrier function in patients with depressed acne scar. Methods A total of 60 patients with depressed acne scar who visited the Department of Dermatology, Zhongshan Tanzhou People's Hospital from January 1 to December 31, 2024 were selected and divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with 1565 nm non-ablative fractional laser, and the observation group was treated with 1565 nm non-ablative fractional laser combined with salicylic acid. The clinical efficacy, skin barrier function, pain and acne scar improvement were compared between the two groups. Results The total effective rate in the observation group (86.67%) was higher than that in the control group (63.33%) (P<0.05). After treatment, the transepidermal water loss, stratum corneum hydration, erythema value, melanin value, sebum and pH in the observation group were better than those in the control group (P<0.05). After treatment, the scores of VAS and ECCA in the observation group were lower than those in the control group (P<0.05). Conclusion The application of 1565 nm non-ablative fractional laser combined with salicylic acid in patients with depressed acne scar has a good effect, which can effectively improve skin barrier function, help to reduce pain, and promote the regression of acne scar. It is worthy of clinical application.