PURPOSE: The purposes of this study were to investigate a treatment strategy to increase liver tumor necrosis and minimize complications with ultrasound-guided percutaneous radiofrequency (RF) ablation and to evaluate its therapeutic efficacy. MATERIALS AND METHODS: A total of 332 patients with 503 liver malignancies underwent RF ablation according to a mathematical protocol with adjunctive measures. In the 332 patients, 205 had 308 hepatocellular carcinomas (HCCs) with a mean largest diameter of 4.1cm and 127 had 195 metastatic liver carcinomas (MLCs) with a mean largest diameter of 3.9cm. In patients with HCC, 60 (29.3%) had stage I/II disease and 145 (70.7%) had stage III/IV disease. Depending on tumor size, shape, and location, a defined treatment strategy was adopted that consisted of a mathematical protocol, an individualized protocol, and adjunctive measures. The mathematical protocol was followed for tumors larger than 3.5cm. The individualized protocol was used for tumors located adjacent to the diaphragm, gastrointestinal tract, or gallbladder. Some adjunctive measures such as supplementary fine needle localization, local saline solution injection, and feeding vessel ablation were used to deal with different features of these liver tumors. Patients were followed regularly to assess treatment efficiency, and the tumor was considered to have early complete necrosis if no viability was found on enhanced computed tomography 1 month after RF ablation. RESULTS: In this series, the early necrosis rates were 95.8% for HCC (295 of 308 tumors), 94.9% for MLC (185 of 195 tumors), 91.3% for tumors larger than 3.5cm (189 of 207 tumors), 90.7% for tumors near the gastrointestinal tract (49 of 54 tumors), 91.5% for tumors near the diaphragm (86 of 94 tumors), and 90.6% for tumors near the gallbladder (48 of 53 tumors). The local recurrence rates were 10.7% for HCC (33 of 308 tumors) and 14.9% for MLC (29 of 195 tumors). The 1-, 2-, and 3-year overall survival rates were 89.6%, 69.4%, and 59.6%, respectively, for HCC and 80.3%, 52.8%,and 30.9%, respectively, for MLC. The 1-, 2-, and 3-year survival rates in 60 patients with stage I/II HCC were 93.7%, 87.1%, and 76.2%, respectively. The incidence of major complications was 1.4% (eight of 574 sessions), which included of three hemorrhages, four injuries to adjacent structures, and one case of needle tract seeding. CONCLUSION: In RF ablation of hepatic tumors, application of a proper protocol and adjunctive measures play important roles in improving tumor necrosis rate and minimizing potential complications.