At the heart of cancer research is the elucidation of oncogenes and tumor suppressor genes (or anti-oncogenes), which has been a driving force in the cancer field for several decades. Most recent studies in this and other labs have revealed dual roles of genes in promoting and suppressing hepatocellular carcinoma (HCC). Deciphering the “paradoxical” effects of these genes may provide a fresh view on the fundamental mechanisms of carcinogenesis, which can lead to development of mechanism-based therapeutics for HCC. Our current focuses are on delineating genetic and epigenetic interactions and cell-cell communications that drive hepatocarcinogenesis. We are very interested in isolating and characterizing cancer stem cells, CSCs (or tumor-initiating cells, TICs) in the liver, and in dissecting the dynamic interplay between tumors and the hepatic microenvironment. Efforts are also being devoted to elucidation of metabolic changes in tumor cells and to search of biomarkers for early diagnosis of liver cancers.