Background: We aimed to assess the diagnostic performance of circulating cell-free DNA (cfDNA) in hepatocellular carcinoma (HCC). Materials & methods: After a systematic literature search bivariate linear mixed models wereused to integrate sensitivity, specificity, positive likelihood ratio, negative likelihood ratioand diagnostic odds ratio. The area under receiver operating characteristics curvesof the included studies was used to estimate the diagnostic value. Results: Thirty-eight articles enrolled in quantitative synthesis. In overall analysis the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristics curves for cfDNA in distinguishing HCC patients from healthy controls were 0.54, 0.90, 5.23, 0.51, 10.27and 0.82, respectively. Conclusion: This study suggests that cfDNA has a promising diagnostic accuracy in detection of HCC.