Hepatocellular carcinoma (HCC) is the third most common malignancy in Korea. Despite recent advances in the area of HCC, a considerable number of HCC patients require non-surgical treatments and systemic therapies because of poor liver function or intermediate to advanced cancer stages at the time of diagnosis. Unfortunately, chemotherapy for advanced HCC has limited response rates and provides a marginal survival benefit. Several studies have supported potential advantages of hepatic arterial infusion chemotherapy (HAIC), designed to improve chemotherapy benefits by increasing the amount of chemotherapy delivered to the site of the tumor and to minimizes the side-effects of the chemotherapy. However, there hasn’t been any report showing different responses between systemic chemotherapy and HAIC for the same patient. Herein, we report a case of HCC showing progressive disease in systemic chemotherapy, but partial response in HAIC with the same regimen for the same patient with portal vein thrombosis. This case implies HAIC might be alternative option for HCC patient showing ineffective response to systemic chemotherapy, even with the same regimen.