Aim To explore the diagnostic efficacy of des-gamma-carboxy prothrombin (DCP) in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). Methods A retrospective study of 459 cases from June 2016 to March 2018 was undertaken, and records of the DCP levels were extracted. The sensitivity, specificity, and cutoff points were calculated using SPSS 17.0 software. A systematic search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials was performed for articles published in English from 1997 to 2017, focusing on serum DCP for HBV-related HCC. Data on sensitivity, specificity, the positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were extracted from five studies by systematic search and one study of our own. The summary receiver operating characteristic (sROC) curve was obtained, and the area under the receiver operating characteristic (AUROC) curve was calculated. Results The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.71 (95% CI: 0.59, 0.80), 0.93 (95% CI: 0.87, 0.96), 9.5 (95% CI: 5.2, 17.5), 0.32 (95% CI: 0.22, 0.46), and 30 (95% CI: 13, 72), respectively. The AUROC curve was 0.91 (95% CI: 0.88, 0.93). Conclusions In the diagnosis of HBV-related hepatocellular carcinoma (HCC), DCP is an ideal marker that should be considered for surveillance purposes.