Abstract: Objective To investigate the clinical effectiveness of aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) on low-grade squamous intraepithelial lesions (LSIL) in the cervix of patients with persistent high-risk human papillomavirus (HR-HPV) infection, and possible immunoinflammatory mechanisms. Methods A total of 200 female patients with histologically confirmed LSIL combined with HR-HPV infection were selected. According to their personal wishes, they were divided into two groups. The research group underwent ALA-PDT treatment, while the control group received CO₂ laser treatment. The patients were followed-up at postoperative 3 and 6 months, where the follow-up items included effectiveness (cytological examination, HPV detection, colposcopy and colposcopic directed biopsy), and safety (adverse reactions). Furthermore, the levels of Toll-like receptor 4 (TLR4) and nuclear transcription factor-κB (NF-κB) in LSIL tissues before treatment and six months after treatment were compared by immunohistochemistry. Results At postoperative 3 and 6 months, the research group showed increases in HR-HPV conversion rate and lesion reversal rate, compared with the control group, whereas the difference was more significant at postoperative 6 months (P<0.05). At postoperative 6 months, no differences were found in the persistence rate, the progression rate, and the recurrence rate of cervical lesions between the research group and the control group (P>0.05). During treatment, patients in the research group reported few adverse reactions, and increased vaginal secretion, lower abdominal discomfort and vulvar itching were the most common symptoms. The difference in the positive expression rates of TLR4 and NF-κB in cervical lesion tissues before and after ALA-PDT treatment was statistically significant (P<0.05). Conclusions ALA-PDT is significantly effective for the treatment of HR-HPV in patients with cervical LSIL, with improvement in the rate of conversion and lesion reversal in comparion with the CO₂ laser control group. One of the immune mechanisms by which ALA-PDT promotes the regression of cervical lesions and the clearance of HPV infections may be related to reduced expression of TLR4 and NF-κB.