A variety of treatments have recently been introduced to improve the prognosis of hepatocellular carcinoma (HCC). These anticancer therapies include the oily carcinostatic agent styrene maleic acid neocarzinostatin (SMANCS). SMANCS is a chemical conjugate of a synthetic copolymer of styrene maleic acid (SMA) and the proteinaceous anti-cancer agent neocarzinostatin (NCS), which dissolves in organic solvents such as pyridine and acetone, and particularly in Lipiodol. NCS is a simple protein capable of inhibiting DNA synthesis and inducing DNA degradation. Lipiodol is an ethyl ester of iodinated poppy seed oil in which most of the unsaturated double bonds in oleic, linoleic and linolenic acid are almost completely iodinated. When a homogeneous suspension of SMANCS with Lipiodol (SMANCS/Lipiodol) is administered intra-arterially, Lipiodol acts as a carrier of SMANCS. Many studies have demonstrated the clinical efficacy of SMANCS/Lipiodol in the treatment of HCC. We have shown that transcatheter arterial infusion (TAI) with SMANCS/Lipiodol has a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of HCC. However, recent clinical studies have indicated that SMANCS causes severe adverse reactions and complications. We have also reported a case of HCC in which multifocal hepatic infarction developed after TAI with SMANCS/Lipiodol. Arterial administration of SMANCS/Lipiodol, therefore, should be given as peripherally as possible via the tumor feeding arteries, to enhance the efficacy of the agent and to reduce the adverse effects.