We report a rare case of spontaneous regression (SR) of hepatocellular carcinoma (HCC). A 70-year-old man consulted us for general fatigue. Enhanced abdominal computed tomography (CT) showed two HCCs, of 5cm in the posterior segment and 8cm around the right Glissonean pedicle with tumor thrombus in the main portal trunk. He refused to undergo any treatment, but 28 months later, CT showed complete disappearance of the hilar tumor and portal tumor thrombus, and partial regression in the posterior tumor with shrinkage of the right lobe of the liver. His PIVKA-II levels decreased from 23358 to 217mAU/ml. In the present case, tumor infarction of the portal thrombus, and the administration of imidapuril hydrochloride and Hochu-ekki-to may have caused SR.