Objective To observe the effect of compound Huangbaiye liniment combined with benzoyl peroxide gel on patients with mild to moderate acne and its effect on skin lesion symptoms. Methods A total of 120 patients with mild to moderate acne who were treated in our hospital from August 2020 to February 2022 were randomly divided into control group and experimental group, with 60 patients in each group. The control group was treated with benzoyl peroxide gel, and the experimental group was treated with compound Huangbaiye liniment combined with benzoyl peroxide gel. The clinical efficacy, skin lesion symptoms and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the experimental group was 95.00%, which was higher than 78.33% in the control group (P <0.05). After treatment, the skin lesion score of the experimental group was lower than that of the control group (P <0.05). The incidence of adverse reactions in the experimental group was 0, which was lower than 8.33% in the control group (P <0.05). Conclusion Compound Huangbaiye liniment combined with benzoyl peroxide gel is effective in patients with mild to moderate acne, which can improve the rate of skin lesion regression, effectively control the symptoms of skin lesions, and the incidence of adverse reactions is small, and the application safety is high.