The current principle of clinical management of cervical high-grade squamous intraepithelial lesion(HSIL) is surgical excision. However excisional procedures of the uterine cervix may have a negative impact on fertility. Topical photodynamic therapy(PDT) is a non-invasive and selective tissue destruction. We investigated the clinical efficacy of PDT for cervical HSIL with high-risk human papilloma virus(HPV) infection.A retrospective study consisting of 96 patients aged 20-50 years with a histologically confirmed cervical HSIL with high-risk HPV infection from July 2018 to June 2022 was carried out. Patients were treated with six times of 20% 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing and colposcopy directed biopsy. Six and twelve months after treatment, TCT and HPV tests were carried out.Three months after 5-ALA PDT treatment, among 96 HSIL with high-risk HPV infection patients, the total lesion regression rate was 89.58%(86/96), and the HPV clearance rate was 79.17 % (76/96) at 3 months follow-up. At 6 and 12 months follow-up, the patients who was HSIL pathological regression and negative HPV at 3 months follow-up continued negative results in both TCT and HPV. All patients with ineffective 5-ALA PDT treatment had persistent HPV infections. There was no significant difference in the HSIL regression rate and HPV clearance rate among different age groups. The main side effects of PDT were abdominal pain and increased vaginal secretions. Univariate analysis showed that the different severity of cervical cytology was associated with lesion regression rate in 5-ALA PDT treatment. The HSIL regression rate of TCT