We report a case of hepatocellular carcinoma (HCC) with a Vp4 tumor thrombus treated successfully with multidisciplinary therapy. A 59-year-old woman who complained of abdominal distension was diagnosed as having HCC associated with hepatitis B virus (HBV) infection. The tumor was located in the left lobe, caudate lobe, and S6, and the tumor thrombus extended into the main portal and right portal veins. Extended left lobectomy with thrombectomy and S6 partial hepatectomy were performed after intrahepatic arterial infusion chemotherapy with radiation. During the surgery, the collateral circulation was preserved for bleeding control and residual liver function preservation. The patient was alive 12 months after surgery. Cases of advanced HCC with Vp4 can be successfully treated by multidisciplinary therapy.