To analyze the factors affecting the prognosis of high risk human papilloma virus (HR-HPV) infection of patients with conization of cervix because of cervical high-grade squamous intraepitheliallesion (HSIL). Methods: From February 2017 to April 2019，229 patients with HR-HPV infection who had undergone cervical conization because of HSIL were selected as subjects. The HR-HPV detection of these patients in the postoperative 6th，12th，18th，and 24th month were performed. Results: The negative conversion rates of HR-HPV infection of the patients in the postoperative 6th，12th，18th，and 24th month were 61.1%, 71.6%, 78.2%, and 84.3%, respectively. The negative conversion rate of HR-HPV infection of the patients with aged ≥40 years old in the postoperative 6th or 12th month was significantly lower than that of the patients with aged <40 years old (P<0.05). There was no significant difference in the negative conversion rate of HR-HPV infection in the postoperative 18th month or 24th month among the patients with different age (P>0.05). There was no significant difference in the negative conversion rate of HR-HPV infection between the patients with single subtype HR-HPV infection and the patients with multiple HR-HPV subtype infection (P>0.05). The negative conversion rate of HR-HPV infection of the patients with 16/18 subtype HR-HPV infection in the postoperative 6th month, 12th month, 18th month, or 24th month was significantly lower than that of the patients with other subtype HR-HPV infection (P<0.05). Age ≥40 years old and 16/18 subtype HR-HPV infection of the patients were the independent risk factors of their postoperative HR-HPV persistent infection (P<0.05). Age ≥40 years old, multiple subtypes HR-HPV infection, and 16/18 subtype HR-HPV infection of the patients had no predictive effect for their HR-HPV persistent infection, and the area under the curve (AUC) of which were 0.549, 0.583, and 0.542, respectively. Conclusion: Age and 16/18 subtype HR-HPV infection of the patients with HSIL are the influencing factors of the negative conversion of the HPV infection after conization of cervix, so the attention should be paid to these patients in clinic and the postoperative follow-up to these patients should be strengthened.