An independent patient cohort was used to assess the performance of the four novel methylation markers together with our two previously validated urinary HCC risk markers, mGSTP1 and mRASSF1a. In this cohort, serum AFP alone has a sensitivity of 29.5% at a high specificity of 95% for detecting HCC at a cut-off of 20 ng/mL, as recommended by the AASLD. Here, AFP is linked to hepatocellular carcinoma.