Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. No more than 30% of HCC patients receive curative treatment. Factors limiting curative therapy include tumor size and degree of liver impairment. Objective: To develop a cure for medium (3.1 - 5.0 cm) and large ( > 5 cm) tumors in seriously impaired livers. Method: Combine radiofrequency ablation (RFA) with lyso-thermosensitive liposomal doxorubicin (LTLD). Results/conclusions: RFA is used safely in patients with medium/large tumors and severe liver impairment; unclear tumor margins limit its curative efficacy. LTLD concentrates in the liver, where the anti-HCC chemotherapeutic, doxorubicin, is released into tumor margins by hyperthermia. RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients.