Hepatocellular carcinoma (HCC) is the fifth most common cancer; advanced hepatic fibrosis is a major risk factor for HCC. Nonalcoholic fatty liver disease (NAFLD) can also progress to cirrhosis and HCC. These liver diseases and their progression are major causes of morbidity and mortality; identification of easily measurable and disease-specific biomarkers is required for early diagnosis and avoidance of invasive diagnostic procedures. Early diagnosis of HCC and assessment of the stage of hepatic fibrosis or NAFLD can also contribute to more effective therapeutic interventions and an improved prognosis. Thus far, we have identified several candidate biomarkers for liver diseases, including HCC and NAFLD, using proteomic technologies. Recent advances in methods for mass

spectrometric analysis, including protein labeling and amino acid analysis, facilitate highly sensitive and exhaustive proteomic analysis of patient samples. In this chapter, we will present an overview of proteomic technologies, including data from our laboratory. Our discussion will focus on the differential analysis of protein expression with the goal of discovering biomarkers for liver disease.