BACKGROUNDPatients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.AIMTo evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH.METHODSThe clinical data of 83 consecutive patients who underwent TIPS combined with I-125 seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up.RESULTSThe success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 & PLUSMN; 7.33 mmHg vs 35.12 & PLUSMN; 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 & PLUSMN; 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 & PLUSMN; 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors (P < 0.05).CONCLUSIONTIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.