Portal vein tumor thrombus (PVTT) is one of the most important clinical characteristics of advanced hepatocellular carcinoma (HCC). The incidence of PVTT has been reported to be 44%-66.2% in patients with HCC who were firstly diagnosed, and 80%-90% were patients with advanced HCC. Once PVTT occurs in patients with HCC, the prognosis is very poor, and the natural survival time is only 2.7-4 months. The current treatment strategy for HCC patients with PVTT remains controversial. Sorafenib is recommended as the only treatment option in Europe and America; and a variety of treatment methods, including surgical treatment, transcatheter arterial chemoembolization, radiotherapy, and systemic chemotherapy, were advocated in Asia. At present, there is no consensus on diagnosis and treatment of HCC with PVTT. Our team has established a multidisciplinary team approach for diagnosis and treatment of HCC with PVTT, and has carried out systematic research and application. This article reviews the molecular mechanism of PVTT in patients with HCC, clinical diagnosis and treatment of PVTT, and the establishment and application of a multidisciplinary team approach.