The diagnostic accuracy of cervical cancer remains a clinical challenge, and a number of studies have used the serum hybrid capture 2 (HC2) human papillomavirus (HPV) DNA in the diagnosis of cervical cancer. The aim of the present meta-analysis was to determine the overall accuracy of HC2 HPV DNA in the diagnosis of cervical cancer. A systematic review of studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Chinese Biomedical Literature Database-disc, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang database was conducted, and the data concerning the accuracy of HC2 HPV DNA in the diagnosis of cervical cancer were pooled. The methodological quality of each study was assessed by quality assessment for studies of diagnostic accuracy (QUADAS). Statistical analysis was performed by employing Meta-DiSc (version 1.4) and Stata (version 12.0) software. The overall test performance was summarized using receiver operating characteristic curves. Finally, 12 studies, including 12,492 subjects, met the inclusion criteria and then included in this present meta-analysis. The summary estimates for serum HC2 HPV DNA in the diagnosis of cervical cancer were as follows: sensitivity 0.83 (95 % confidence interval (CI) 0.81-0.85), specificity 0.71 (95 % CI 0.69-0.72), positive likelihood ratio 3.65 (95 % CI 1.77-7.54), negative likelihood ratio 0.32 (95 % CI 0.21-0.48), and diagnostic odds ratio 10.54 (95 % CI 4.95-22.46), and the area under the curve was 0.8922. Our findings suggest that HC2 HPV DNA may improve the accuracy of cervical cancer diagnosis, while the results of HC2 HPV DNA assays should be interpreted in parallel with conventional test results and other clinical findings.