Objective To explore the clinical effect of ultra-pulsed CO2 lattice laser combined with small needle knife subcutaneous peeling in the treatment of acne depressed scar. Methods From August 2020 to October 2021, 76 patients with acne depressed scar admitted to the dermatology department of our hospital were selected as the research objects. According to the random number table method, they were divided into control group and observation group, with 38 cases in each group. The control group was treated with single ultra-pulsed CO2 lattice laser, and the observation group was treated with ultra-pulsed CO2lattice laser combined with small needle knife subcutaneous peeling. The clinical efficacy, scab time, erythema duration, acne scar weight score (ECCA), inflammatory factor level, treatment satisfaction and adverse reactions were compared between the two groups. Results The total effective rate of the observation group was higher than that of the control group (PP<0.05). The total satisfaction of the observation group was higher than that of the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, but the differerue was not statistically significant (P﹥0.05). Conclusion The clinical effect of ultra-pulsed CO2 lattice laser combined with small needle knife subcutaneous peeling in the treatment of acne depressed scars is good, which can effectively improve the scar symptoms of patients, shorten the treatment time, control the inflammatory response, promote the rapid recovery of patients, improve patient satisfaction, and have fewer adverse reactions and higher safety.