In two pivotal randomized controlled trials, sorafenib, as compared to placebo, has been demonstrated to yield a significantly favorable disease control rate, and also favorable prolongation of progression-free survival and overall survival in patients with advanced hepatocellular carcinoma. At present, it is acknowledged as a standard treatment for advanced hepatocellular carcinoma and is available worldwide. Some randomized controlled trials performed to clarify the usefulness of adjuvant therapy after local treatment, including surgical resection, local ablative therapy and transcatheter arterial chemoembolization for hepatocellular carcinoma are ongoing. In addition, a number of new molecular -targeted agents and combined therapies are under development. On the other hand, intra-arterial chemotherapy, such as with 5-fluorouracil and cisplatin, 5-fluorouracil and interferon, and cisplatin alone, has been widely used for advanced hepatocellular carcinoma in Japan, because of the high response rates and favorable overall survival in advanced hepatocellular carcinoma patients. Survival benefit has, however, not been demonstrated in well-designed randomized controlled studies. It is important to clarify the appropriate candidates, proper treatment method and survival benefit of intra-arterial chemotherapy. After the introduction of sorafenib, chemotherapy for advanced hepatocellular carcinoma has been changing remarkably, and further improvements of chemotherapy for hepatocellular carcinoma are expected.