Objective: The objective of this study is to further clarify the correlation between colorectal cancer (CRC) and human papillomavirus (HPV) through literature search and meta-analysis, which is conducive to the formulation of further prevention programs. Methods: Searching Web of Science, PubMed, MEDLINE, Scopus, and CENTRAL for studies investigating the relationship between CRC and HPV. All analyses were performed through Revman (version 5.3, the Cochrane Collaboration, Oxford, UK). Data from selected studies were extracted into two by two tables. Moreover, all included studies were weighted and summarized. Results: Eighteen studies were included. The expression of HPV in CRC tissues was obviously higher than that in nonmalignant tissues (odds ratio [OR] = 5.56, 95% confidence interval [CI] = 3.18-9.72, Z = 6.02, P < 0.00001). The expression of HPV in CRC tissues and adenoma tissues showed no significant abnormalities (OR = 1.74, 95% CI = 0.92-3.29, Z = 1.70, P = 0.09). The expression of HPV in CRC tissues was obviously higher than that in normal tissues (OR = 7.23, 95% CI = 3.89-13.42, Z = 6.27, P < 0.00001). Conclusion: HPV infection in CRC tissues was obviously higher than that in nonmalignant tumor tissues and normal colon tissues, but there were no statistically significant abnormalities between CRC tissues and adenoma tissues.