Objective:To investigate the clinical efficacy of salicylic acid antibacterial gel combined with doxycycline and Runzao Zhiyang Capsules in the treatment of moderate-to-severe acne. Methods: A total of 98 patients with moderate-to-severe acne admitted from January to December 2025 were selected and divided into a control group and an observation group using a random number table method. The control group received doxycycline combined with Runzao Zhiyang Capsules, while the observation group additionally received topical salicylic acid antibacterial gel. The clinical outcomes of the two groups were compared.? Results: After 8 weeks, the total effective rate was higher in the observation group than in the control group (87.76% vs. 71.43%, P<0.05). Baseline indicators were comparable between groups (P>0.05). After 8 weeks, inflammatory lesion count [(8.52±2.41) vs. (12.94±3.16)], non-inflammatory lesion count [(12.37±3.25) vs. (17.85±4.02)], IGA score [(1.42±0.38) vs. (2.05±0.47)], sebum level [(112.53±18.64) vs. (139.26±20.17) μg/cm2], and NRS score [(2.11±0.76) vs. (3.47±0.92)] were lower in the observation group (P<0.05). The incidence of adverse reactions was 12.24% in both groups, with no significant difference (P>0.05). Conclusion: Salicylic acid antibacterial gel combined with doxycycline and Runzao Zhiyang Capsules can improve clinical efficacy, reduce the number of skin lesions, decrease sebum secretion, and alleviate pruritus in patients with moderate-to-severe acne, with favorable safety.