Gene expression profiling using microarray technologies provides a powerful approach to understand complex biological systems and the pathogenesis of diseases. In the field of liver cancer research, a number of genome-wide profiling studies have been published. These studies have provided gene sets, that is, signature, which could classify tumors and predict clinical outcomes such as survival, recurrence, and metastasis. More recently, the application of genomic profiling has been extended to identify molecular targets, pathways, and the cellular origins of the tumors. Systemic and integrative analyses of multiple data sets and emerging new technologies also accelerate the progress of the cancer genomic studies. Here, we review the genomic signatures identified from the genomic profiling studies of hepatocellular carcinoma (HCC), and categorize and characterize them into prediction, phenotype, function, and molecular target signatures according to their utilities and properties. Our classification of the signatures would be helpful to understand and design studies with extended application of genomic profiles. © 2011 Wiley-Liss, Inc.