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 their invasion to surrounding tissues. We report a case of complete regression of advanced HCC during COX-2 inhibitor administration. An eighty-year-old female was diagnosed as advanced hepatocellular carcinoma (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 was completely disappeared without specific treatment for the HCC, and the size of mass markedly decreased on follow-up CT scan.