Significance
We report comparative plasma proteome profiles of HBV-associated HCC and nonmalignant chronic liver diseases, including chronic hepatitis B and cirrhosis. The quantification of these datasets showed altered abundance of 21 proteins in HBV-related HCC and provides a reference point for future applied and basic research. In addition, we have demonstrated that the candidate protein vWF is involved in the pathogenesis of HBV infection and replication, and also associated with clinicopathologic staging of HCC patients with HBV infection. Overall these findings provide information on the mechanism of HCC development, which may assist in the development of novel cancer and HBV therapeutic drugs.