Abstract： Objective： To observe the effect of Guben Jiedu Decoction combined with Recombinant Human Interferon α- 2a Vaginal Suppository on cervical high- risk human papillomavirus (HPV) infection of spleen deficiency with damp-heat type and vaginal microenvironment of the patients. Methods：A total of 90 cases of patients with cervical high-risk HPV infection of spleen deficiency with damp-heat type were included and divided into two groups according to the random number table method，with 45 cases in each group. The control group was treated with Recombinant Human Interferon α-2a Vaginal Suppository，and the treatment group was treated with Guben Jiedu Decoction based on the treatment of the control group. Both groups were given 3 consecutive courses of treatment； during each treatment course， the two groups received medication 3 days after the end of menstrual period，and stopped taking medication after 18 days of treatment. Before treatment and after 3 courses of treatment，the traditional Chinese medicine (TCM) syndrome scores were evaluated，and the negative conversion rates of HPV，the reversal rates of low- grade squamous intraepithelial lesions (LSIL)， and the recovery of vaginal microenvironment were calculated. The clinical effects in the two groups were compared. Results： After treatment， the total effective rate， the negative conversion rate of HPV， the reversal rate of LSIL， and the rate of vaginal microenvironment back to normal in the treatment group were higher than those in the control group (P＜ 0.05). TCM syndrome scores in the two groups were decreased when compared with those before treatment (P＜0.05)， and the TCM syndrome score in the treatment group was lower than that in the control group (P＜0.05). The vaginal pH value in the treatment group was lower than that in the control group (P＜0.05). Conclusion： Guben Jiedu Decoction combined with Recombinant Human Interferon α- 2a Vaginal Suppository has a significant curative effect in the treatment of patients with cervical high-risk HPV infection of spleen deficiency with damp- heat type and can help relieve symptoms and signs， promote HPV negative and LSIL reversal，and improve the vaginal microenvironment.