Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocarcinogenesis. Inhibitors of COX-2 have proapoptotic and antiproliferative effects on malignant tumors and inhibit tumor invasion to the surrounding tissues. We report here a case of complete regression of advanced hepatocellular carcinoma (HCC) during COX-2 inhibitor administration. An eighty-year-old female was diagnosed as an advanced HCC, which was associated with HCV infection. She received COX-2 inhibitor for 3 months due to degenerative arthritis of both knees. Tumor enhancement on arterial phase CT completely disappeared without specific treatment for the HCC, and the tumor size decreased on the follow-up CT scan. (Korean J Hepatol 2006; 12:449-454)