Spontaneous regression of hepatocellular carcinoma is an extraordinarily unusual phenomenon. We present here a case of a 75-year-old man in whom multiple lung metastases of hepatocellular carcinoma regressed spontaneously. He underwent systemic chemotherapy for hepatocellular carcinoma with multiple lung metastases. However, the chemotherapy was not effective and he was therefore followed up without any anticancer treatments in an outpatient clinic. Four months later, multiple lung nodules regressed dramatically and the serum alpha-fetoprotein level decreased markedly. After an 8-month period of the regression, however, intrahepatic lesions gradually enlarged, although multiple lung metastatic lesions remained regressed. The mechanisms underlying this intriguing phenomenon remain unknown.