Abstract Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.