Rapid intrahepatic and distant metastasis of hepatocellular carcinoma (HCC) after locoregional treatment for early stage tumor is very rare. Descriptions of spontaneous regression of HCC exist in case reports, but its true mechanism is unclear. Here, we describe a case of rapid dissemination with lung metastasis shortly after localized RFA treatment of HCC liver lesions, followed by spontaneous, sustained regression of those lung lesions. We also show the detection of cytotoxic T lymphocytes (CTLs) specific to hepatitis B antigens by immune assay in this patient. We propose immune-related destruction as the basis for spontaneous regression.