HBV infection is the major cause of the development of hepatocellular carcinoma (HCC). HCC is one of the most common malignancies in the world. The morbidity rate associated with HCC is mainly linked to late diagnosis. Thus, it is very important to discover prognostic factors that can act as biomarkers for preventing HCC development, and those that can act as therapeutic targets. Proteomics analysis has been applied to identify biomarkers from clinical HCC samples. In addition, the cell-based HBV replication and viral protein overexpression system, which provides a model of the cell at an early stage of viral infection, was also used to identify biomarkers. The proteins identified at this stage may be relevant to HBV-associated HCC prognosis. In this review, we discuss the current status of proteomics analysis in the discovery of cellular proteins and prognostic HCC biomarkers, with a special focus on cell metastasis and angiogenesis.