Hepatitis, liver cirrhosis and liver cancer are major liver diseases particularly in Asia. Liver cancer is also one of the leading cancers causing death in the world. Cyclooxygenase 2 (COX-2) is a highly inducible and key rate-limiting enzyme involved in the production of prostaglandins (PGs), prostacyclin, and thromboxanes. COX-2 is expressed in response to a variety of proinflammatory agents and cytokines. COX-2 is associated with liver pathogenesis, including fibrosis and cancer. It has been shown that COX-2 is up-regulated in cirrhotic tissues adjacent to hepatocellular carcinoma (HCC) and well-differentiated HCC. We and others also observed the up-regulation of COX-2 in liver fibrosis. The chemopreventive efficacy of COX-2 inhibitors in liver fibrosis and hepato-carcinogenesis has been observed in animal experimental models. COX-2 inhibitors have also exhibited significant anti-proliferative effects on HCC cell lines by inducing apoptosis and cell cycle arrest and blocking growth signaling pathways. These results raise the possibility that COX-2 may be a target for the prevention or treatment of liver fibrosis, hepato-carcinogenesis and liver cancer, as it is for colon cancer. In this article, we review recent studies on the role of COX-2 in liver fibrosis and liver cancer, and discuss rationale and feasibility of COX-2 inhibitors in chemoprevention and treatment of liver fibrosis and liver cancer.