The aim of this study was to determine the plasma levels of vitamin K-dependent protein growth arrest-specific protein 6 (Gas6) and its soluble receptor Axl (sAxl) in patients with hepatocellular carcinoma (HCC), acute hepatitis (AH), fulminant hepatitis(FH), chronic hepatitis (CH), and liver cirrhosis (LC) and to determine whether Gas6 and sAxl can be used as biomarkers. Immunoassys were used to measure levels of plasma Gas6 and sAxl in 40 patients with HCC, 13 patients with AH, 3 patients with FH, 7 patients with LC, and 20 healthy normal adult controls (NC). Furthermore, urinary γ-carboxyglutamic acid (Gla) was measured by high performance liquid chromatography. We have addressed this issue by conducting a cross-sectional study to determine whether plasma Gas6 and sAxl levels are associated with DCP, urinary γ-Gla, and liver functions in humans. Levels of Gas6, sAxl, and γ-Gla were significantly higher in HCC as compared to those in NC, and they were significantly positive correlated. Gas6/sAxl molar ratios in HCC were significantly higher than in NC, but those ratios in AH, FH, and LC were significantly lower in NC. Furthermore, Gas6/sAxl molar ratios in HCC increased significantly in comparison with those AH and LC. The increase of Gas6, sAxl and Gas6/sAxl molar ratio were correlated with the progression and poor prognosis of HCC. Thus, Gas6 and sAxl may be useful biomarkers for HCC.