Objective: To explore the changes of serum hyaluronic acid (HA), transforming growth factor-β1 (TGF-β1) and interferon-γ/interleukin-4 (IFN-γ/IL-4) in patients with cervical low-grade squamous intraepithelial lesion (LSIL) before and after 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and analyze their predictive value on recurrence. Methods: A total of 100 patients with cervical LSIL were included and treated with ALA-PDT. They were divided into an effective group (n=84) and an ineffective group (n=16) based on the HPV negative conversion after 6 months of treatment. The patients in the effective group were followed up for another 6 months and divided into a recurrence group (cytology≥ASC-US and HPV positive, n=15) and a non-recurrence group (HPV negative, n=69) based on the results at the end of follow-up. Serum levels of HA, TGF-β1, and IFN-γ/IL-4 ratio were compared between the two groups before and after treatment. Demographic data and cervical LSIL characteristics were collected. Univariate and multivariate Logistic regression analyses were used to identify independent risk factors for recurrence, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of changes in serum markers before and after treatment for recurrence. Results: At the end of treatment, HA and TGF-β1 levels in effective group were lower than those in ineffective group (P<0.05) while IFN-γ/IL-4 level was higher (P<0.05). The levels of HA and TGF-β1 in the non-recurrent group were lower than those in the recurrent group (P<0.05), the ratio of IFN-γ/IL-4 was higher than that in the recurrence group (P<0.05). Univariate and multivariate Logistic regression analyses showed that the HA change value and TGF-β1 change value were independent risk factors for recurrence after ALA-PDT in patients with cervical LSIL, while IFN-γ/IL-4 change value was an independent protective factor (P<0.05). The AUCs of the aforementioned factors for predicting recurrence after ALA-PDT were 0.862, 0.843 and 0.754, and the sensitivities were 73.33%, 80.00% and 66.67%, respectively, and the specificities were 92.75%, 79.71% and 86.96%, respectively (P<0.05). Conclusion: ALA-PDT can achieve good efficacy in the treatment of cervical LSIL, reduce the levels of serum HA and TGF-β1, and increase the IFN-γ/IL-4 ratio. The changes of the above indexes before and after treatment are independently related to the risk of recurrence. Early detection of the above indexes can provide guidance for clinical diagnosis and treatment.