Our previous study suggested that the serum-derived hyaluronan associated protein (SHAP)-hyaluronan (HA) complex in the sera of patients with rheumatoid arthritis is useful as a marker that directly correlates with the degree of inflammation. Here, we have investigated the serum levels of the SHAP-HA complex in patients at various clinical stages of chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) caused by infection with the hepatitis C or hepatitis B virus. Both serum levels of the SHAP-HA complex and HA in those patients were significantly higher than those of the controls and increased in the order of CH<LC<HCC. Different from the HA levels, there was a significant difference in the SHAP-HA complex levels between the LC and HCC groups in both HBV- and HCV-infected patients. In addition, the serum level of the SHAP-HA complex correlated with the well-known biomarkers for liver injury and function such as albumin and platelet, including the HCC indicator alpha-fetoprotein. In conclusion, the present data suggest that the SHAP-HA complex level is a better indicator for the progression of the stages of liver fibrosis, and that it could be a marker for HCC, in both HBV- and HCV-infected patients.