BACKGROUNDMain portal vein tumor thrombus (MPVTT), which has a high incidence, is the major complication of terminal liver cancer. The occurrence of MPVTT is always a negative prognostic factor for patients with hepatocellular carcinoma (HCC). Therefore, attention should be paid to the treatment of MPVTT and its complications.AIMTo evaluate the efficacy of transarterial chemoembolization/transarterial embolization (TACE/TAE)+125I seeds implantation with transjugular intrahepatic portosystemic shunt (TIPS) in treating MPVTT and its complications.METHODSFrom January 2007 to March 2015, 85 consecutive patients with MPVTT were nonrandomly assigned to undergo treatment with TACE/TAE + TIPS and 125I implantation (TIPS-125I group) or TACE/TAE + TIPS only (TIPS only group) in Beijing Shijitan Hospital, and all clinical data were collected. During 24 mo follow-up, the incidence of overall survival, stent stenosis and symptom recurrence was analyzed to evaluate the efficacy of TIPS-125I.RESULTSDuring 24 mo follow-up of all patients, we collected data at 6, 12 and 24 mo. The rates of survival were 80%, 45%, and 20%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 64.4%, 24.4%, and 4.4%, respectively (P < 0.05). The rates of symptom recurrence were 7.5%, 22.5%, and 35%, respectively, in the TIPS-125I group, whereas those in the TIPS only group were 31.1%, 62.2%, and 82.2% (P < 0.05). The rates of stent restenosis were 12.5%, 27.5%, and 42.5%, respectively, in the TIPS-125I group, and 42.2%, 68.9%, and 84.4%, respectively, in the TIPS only group (P < 0.05). TIPS-125I was found to be significantly favorable in treating MPVTT and its complications in patients with HCC.CONCLUSIONTACE/TAE+125I combined with TIPS is effective in treating MPVTT and its complications, improving quality of life of patients and reducing mortality.