ObjectiveTo summarize recent advances, clinical applications, and future directions of the portal vein iodine-125 (125I) irradiation stent in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). MethodsLiterature published over the past 15 years concerning 125I irradiation stents for HCC with PVTT treatment was retrieved. Studies focusing on stent design, radiation dosimetry, combination treatment strategies, and prognostic outcomes were systematically reviewed and analyzed. ResultsThe portal vein 125I irradiation stent provides dual therapeutic benefits: mechanical recanalization of the obstructed portal vein and continuous intraluminal low-dose γ-radiation, achieving high-dose, long-duration localized irradiation. Clinical evidences indicate superior outcomes in maintaining portal vein patency, controlling tumor thrombus progression, and improving overall survival as compared with transcatheter arterial chemoembolization (TACE) or systemic therapy alone. Moreover, combination approaches with TACE or targeted or immunotherapy further enhance tumor control and survival benefits, making it an integral part of multidisciplinary HCC management. ConclusionsAs an innovative integration of interventional and brachytherapy techniques, the 125I portal vein irradiation stent shows promising efficacy and safety in treating HCC with PVTT. Future developments should emphasize biomaterial optimization, image-guided precision implantation, and individualized dosimetry, supported by multicenter randomized controlled trials to establish standardized therapeutic protocols and advance precision oncology.