Objective To study the efficacy of percutaneous ablative therapy for malignant liver lesions under real-time virtual guidance. Methods Percutaneous ablations were applied to 76 patients with 125 malignant liver lesions under the guidance of a real time virtual system (RVS). 64. 8% (81/ 125) lesions were undetectable on conventional ultrasound (US). The time spent on image fusion and the local treatment response were studied. Results The average time taken to synchronize the ultrasound and CT images was (19. 2±12. 8) min (range 5~55 min). Complete ablations were achieved in 86. 4% (38/44) of distinctly visualized lesions and in 91. 6% (74/81) of poorly visualized lesions on US. No treatment associated complications were found. Conclusion Ablation assisted by RVS and CT was safe and efficacious, especially for lesions undetectable by conventional ultrasound.