To clarify the relationship between NHEJ genes and the prognoses of patients with HCC, we constructed a novel prognostic risk score based on six NHEJ genes: DCLRE1C, FEN1, PRKDC, XRCC4, XRCC5 and XRCC6. The risk score was used to stratify HCC patients into tow risk categories and predicted their prognosis based on the TCGA database, and then was validated in the GEO cohort. This evidence concerns the gene XRCC6 and hepatocellular carcinoma.