Abstract: Objective To evaluate the relationship between HPV infection and the disease-free survival (DFS) of oropharyngeal cancer (OPC) patients. Methods Databases including CNKI, VIP, Wanfang data and PubMed were searched for relevant studies on HPV infection and OPC prognosis. According to the inclusion and exclusion criteria, these studies were screened, and the merging relative risk ratio (HR) and 95% confidence interval (95%CI) were calculated. Results A total of 16 qualified articles were involved, including 2 512 OPC patients (1 210 cases of HPV positive and 1 302 cases of HPV negative). HPV positive rate was 48.17%. Compared with HPV negative patients, HPV infection had a protective effect on the recurrence or metastasis of OPC (HR: 0.371, 95%CI: 0.231-0.511); the single type of HPV-16 infection had lower risk of DFS of OPC (HR: 0.248, 95%CI: 0.132-0.365). Simultaneous HPV16 positive and p16 overexpression was inversely related with the low risk of recurrence or metastasis of OPC (HR: 0.281, 95%CI: 0.137-0.424). Conclusion HPV infection may be a beneficial factor for the DFS of oropharyngeal cancer patients.