Objective To explore the effect of fractional laser combined with silicone gel on skin lesion condition and skin barrier function in patients with post-acne depressed scar. Methods A total of 70 patients with post-acne depressed scar admitted to Dingtao District Rangu Town Central Health Center from January 2022 to June 2023 were selected as the research subjects. 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 laser, and the observation group was treated with fractional laser combined with silicone gel. The skin lesion condition, skin barrier function, treatment effect and recovery time were compared between the two groups. Results After treatment, the scores of acne, pimples, nodular cysts and pustules in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). After treatment, the transepidermal water loss and sebum content in the observation group were lower than those in the control group, while the skin water content was higher than that in the control group (P<0.05). The total effective rate of treatment in the observation group was 100.00%, which was higher than 85.71% in the control group (P <0.05). The incrustation time, decrustation time and healing time in the observation group were all shorter than those in the control group (P <0.05). Conclusion The application of fractional laser combined with silicone gel in patients with post-acne depressed scar can improve the skin lesion condition and skin barrier function, which is beneficial to improving the treatment effect and shortening the recovery time, with definite clinical application value.