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This study compares the diagnostic capability of Protein induced by vitamin K absence or antagonist-II (PIVKA-II) with alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC). The study conducted a systematic literature search to identify relevant studies published up to December 20, 2017. A total of 31 studies were included, and the data were analyzed using a random effects model. This meta-analysis indicates that PIVKA-II is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.