To explore the interaction between the high-risk human papillomavirus (HR-HPV) infection of women with cervical lesions and their vaginal microecological changes. Methods: The clinical data of the women who had been given cervical thinprep cytologic test (TCT) in the hospital from January 2023 to January 2024 were selected in this study retrospectively. 102 women with positive result of TCT were in the observation group and the other women with negative result of TCT were in the control group. The cervical lesions was graded by the Bethesda 2014 version reporting system. The HR-HPV infection status and the vaginal microecological indicators of the women in the two groups were detected. Logistic regression was used to analyze the correlation between the HR-HPV infection status of the women with different grade of the cervical lesions and their vaginal microecology. Results: There were no statistically significant differences in the cleanliness, the positive rates of Gardnerella, Trichomonas and fungi, the pH value, the abnormal rates of hydrogen peroxide, sialidase and acetylglucosaminidase of the women between the two groups (P>0.05). The positive rate of bacterial vaginosis, the abnormal lactobacilli rate, the positive rates of leukocyte esterase and HR-HPV of the women had significant differences between the two groups (P<0.05), and which increased with the aggravation of the cervical lesions of the women (P<0.05). Logistic regression analysis showed that there were interaction between the HP-HPV infection of the women with different grade of the cervical lesions and their lactobacillus status (OR=18.138, 95%CI 4.288-76.726), bacterial vaginosis (OR=13.483, 95%CI 3.042-59.758) and leukocyte esterase (OR=7.117, 95%CI 1.918-26.413) (P<0.05). Conclusion: There were interaction between the vaginal microecological change of the women with cervical lesions and their HR-HPV infection, so improving the vaginal microecological environment of the women is of great significance for the prevention of their cervical cancer.