Abstract: OBJECTIVE To investigate the factors related to the natural clearance and persistent infections of high-risk human papillomavirus (HR-HPV) infections, so as to provide references for clinical treatment. METHODS A total of 428 cases of patients with positive HR-HPV from Jan. 2013 to Jan. 2014 in our hospital gynecological department were selected, and were followed up for 1 time every 3~6 months for continuous 3 years, and totally 402 patients completed follow-up. Spontaneous clearance of HR-HPV patients was observed, and the relationships between single and multiple virus infections, genotypes, age with virus removal and persistent infections were analyzed. RESULTS There was some difference in the persistent infection rate of different high-risk HPV infections. The HPV infection rates of single high-risk HPV infections, multiple high-risk HPV infections, and mixed infections were 22.19%, 41.46%, and 37.50%, and the difference was significant (P<0.05). The persistent infections were mainly HPV 16, 18 and 51. The viral clearance time of single high-risk HPV infection, multiple high-risk HPV infections, and mixed infections were (12.87±0.43) months, (17.85±0.76) months, and (15.23±0.45) months, respectively, and the difference was significant (P<0.05). The group of patients with age > 50 years old had the highest rate of persistent infections, which was significantly higher than other groups (P<0.05). In 329 cases of high-risk HPV positive patients, the number of viral clearance gradually increased with the increase of the number of follow-up years, and the number of corresponding persistent infections decreased year by year. CONCLUSION Spontaneous clearance and persistent infections of HR-HPV infection are affected by single or multiple infections and infection genotypes, and the persistent infection rate of multiple HR-HPV is higher than that of single HR-HPV infections, and the virus clearance time is longer.