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Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients’ survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C‐index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery. [ABSTRACT FROM AUTHOR]