A 33-year-old man presented with pain and palsy of the leg in 2008 for treatment of hepatocellular carcinoma with huge distant metastases. The patient's tumors had slowly enlarged despite several treatments. Oral administration of sorafenib at 800 mg/day with careful observation was commenced in 2009. Laboratory investigations on day 7 showed massive tumor lysis. An abdominal CT showed multiple low density areas and tumor markers decreased, indicating extended tumor necrosis. In conclusion, clinicians should bear in mind not only the published adverse effects, but also massive tumor lysis, when treating patients with large tumor burden by sorafenib.