Serum sCD163, IL-10, IL-12 and peripheral Cldn1 and TGF-β expression levels represent novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts. The gene discussed is CLDN1; the disease is hepatocellular carcinoma.