We report four patients with hepatocellular carcinoma (all men, with liver cirrhosis and hepatitis C virus infections) who showed spontaneous regression of the tumor. When the spontaneous regression occurred all of the patients were over age 67 years. They showed a rapid increase of serum alpha-fetoprotein levels just before the spontaneous regression of hepatocellular carcinoma. In all the patients, the alpha-fetoprotein level decreased to within normal limits and the tumor was partially to completely reduced in size. One patient revealed regression after bleeding of esophageal varices and blood transfusion. Another showed spontaneous regression after taking several complementary and alternative medicines. However, the mechanisms underlying this intriguing phenomenon remain unknown.