We have established a single catheter technique of percutaneous isolated liver perfusion using a 4-lumen-2-balloon (4L - 2B) catheter for treatment of unresectable malignant liver tumors. Herein reported are the technique, safety and pharmacokinetics of the system in comparison with the original double-balloon technique. This study included 19 patients with malignant liver tumors treated by adriamycin at a dose of 100 mg/m2. Seven patients had the double-balloon technique (group D), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other 12 patients had single catheter technique (group S). In group S, hepatic effluent was solely isolated and directed to CHP filters. All patients except for one in group S showed good hemodynamic stability. The hepatic venous flow rate of group S was significantly higher than in group D (p < 0.05). Although the mean area under the time concentration curve at systemic serum was significantly lower in group S compared to group D, the rate of side effects was similar in both groups. A 4L. 2B single catheter allowed safe and repeated percutaneous isolated liver perfusion for technical simplification of the treatment.