Objective To evaluate the combination use of transcatheter arterial chemoembolization (TACE), portal vein embolization (PVE) and high intensity focused ultrasound (HIFU) in treating portal vein tumor thrombus(PVTT). Methods A total of 85 patients with primary hepatocellular carcinoma complicated by PVTT, who were encountered during the period from Jan. 2011 to Feb. 2012 at authors’ hospital, were enrolled in this study. The patients were divided into the study group (n=47) and the control group (n=38). TACE, PVE and HIFU were performed in the patients of the study group, while only TACE and PVE were carried out in the patients of the control group. The therapeutic process was as follows: PVE was carried out 2 weeks after TACE was performed, and for the patients of the study group additional HIFU was conducted about 10 days after PVE procedure. Results The short-term effective rate in the study group and the control group was 89.4% (42/47) and 39.5% (15/38) respectively, and the difference between the two groups was statistically significant (P< 0.05). The 6-month, one-year, and two-year survival rate in the study group were 87.2%(41/47), 66.0%(31/47) and 27.7%(13/47) respectively; the median survival time was 15.4 months. In the control group, the 6-month, one-year, and two-year survival rate were 55.3% (21/38), 39.5% (15/38) and 10.5%(4/38) respectively;the median survival time was 10.3 months. The differences between the two groups were statistically significant (P< 0.05). Conclusion For the treatment of primary hepatocellular carcinoma associated with portal vein tumor thrombus, transcatheter arterial chemoembolization, portal vein embolization together with high intensity focused ultrasound is an safe and effective therapy as it can significantly improve the therapeutic effect and prolong the survival time.