Treatment option for liver cancer patients with large tumor >5 cm and/or portal vein tumor thrombosis is very limited. New treatment strategy is badly needed. Our study is to determine the safety and treatment efficacy of a new minimally invasive treatment strategy-liver segment thermal ablation.Late-stage hepatocellular carcinoma patients were included and treated with percutaneous ablation to destroy the entire tumor-containing liver segment to reduce reoccurrence and prolong survival. Transcatheter arterial chemoembolization was used before ablation to label tumor margin. The patients were followed up routinely.The patients were followed up for 8 to 95 months. Mean overall survival (OS) (n = 6) was 21.5 months (range 8-95). For patients in BCLC stage B (n = 2), average OS was 16 months; for those in stage C (n = 4), mean OS was 25 months (range 15-95). Out of all 6 patients, 2 reoccurred within 1 year, and 1 reoccurred after 13 months postoperatively. The average alpha-fetoprotein was dropped from 1153.69 to 41.22 μg/L postoperatively. No severe intra or postoperative complications were observed.Our preliminary data indicated that transcatheter arterial chemoembolization + segment ablation is safe and benefits survival significantly for late-stage hepatocellular carcinoma patients. A prospective multicenter, randomized trial comparing focal and segment ablation is now ongoing in China (Trial Registry Number, ChiCTR-TRC-12002786).