Objective To explore the effect of fractional CO2 laser combined with topical growth factors on aesthetic effect in patients with atrophic acne scar. Methods A total of 76 patients with atrophic acne scar admitted to Suyu District People's Hospital from May 2024 to July 2025 were selected. According to the random number table method, they were divided into the control group (n=38) and the observation group (n=38). The control group was treated with fractional CO2 laser, and the observation group was treated with fractional CO2 laser combined with topical growth factors. The aesthetic effect, local skin physiological function indexes, skin symptom improvement time and adverse reactions were compared between the two groups. Results After treatment, the scores of ECCA and skin melanin index in the observation group were lower than those in the control group (P<0.05). After treatment, the transepidermal water loss, stratum corneum protein content, stratum corneum hydration and skin sebum secretion in the observation group were better than those in the control group (P<0.05). The pain duration, erythema duration, decrustation time and local skin crusting time in the observation group were shorter than those in the control group (P<0.05). The incidence of adverse reactions in the observation group was 5.26%, which was lower than 21.05% in the control group (P<0.05). Conclusion Fractional CO2 laser combined with topical growth factors has a deffnite aesthetic effect in the treatment of patients with atrophic acne scar. It can improve skin physiological functions, shorten the improvement time of skin symptoms, and reduce the incidence of adverse reactions.