We describe the case of a 68-year-old man who presented with a massive lesion in the right liver. It was confirmed by preoperative aspiration biopsy to be a case of moderately differentiated hepatocellular carcinoma, and the patient was shown by immunohistochemistry to have a mutation in the p53 gene. The hepatic lesion showed complete necrosis after arterial embolization combined with microwave ablation. During a re-examination 3 months after ablation, the α-fetoprotein level was found to have increased markedly. Bilateral pulmonary metastases were shown by a lung computed tomography scan, with a focal diameter smaller than 1 cm. Hepatic and bronchial intra-arterial infusion with the recombinant adenovirus p53 gene (rAd-p53) was performed twice. The second time the infusion was administered, interleukin-2 was used in combination with rAd-p53. After 2 months of treatment, the bilateral pulmonary lesions had almost disappeared. After 7 months of treatment, the bilateral pulmonary metastases disappeared completely, and no further recurrence has been identified in the lungs and liver.