Background: Persistent high-risk human papillomavirus (hrHPV) infection is a crucial cause of cervical cancer, for which optimal pharmacological intervention remains unavailable. This study aimed at evaluating the therapeutic efficacy of REBACIN® in patients with persistent hrHPV infection.Methods: This study is a combination of a retrospective analysis and a meta-analysis. The retrospective analysis included 364 patients who were persistently infected with HPV for at least twelve months, between September 2015 and February 2019, and only received REBACIN® intervention. HPV DNA typing, HC2 hrHPV DNA, and ThinPrep cytologic tests were performed before and after REBACIN® intervention, to evaluate the therapeutic efficacy. The meta-analysis included trials evaluating the therapeutic efficacy of interferons.Results: After a follow-up period of three to six months, the overall effective rate of REBACIN® was 74.73% (272/364), which was higher than that of interferon (61.50%). The efficacy of REBACIN® was correlated with HPV type (OR: 0.549, 95% CI: 0.367–0.822, P < 0.05) and pretreatment cytology (OR: 0.358, 95% CI: 0.173–0.739, P < 0.05).Conclusions: REBACIN® is potently efficacious at clearing persistent hrHPV infection; hence, it can serve as an optional intervention for persistent hrHPV infection.