Locally advanced or metastatic pancreatic cancer has been a long-term challenge to clinicians, due to the poor overall survival rate compared with that of other gastrointestinal malignancies. Recently, with the emerging applications of therapeutic endoscopic ultrasonography (EUS), EUS- guided fine needle injection with antitumor agents is considered a promising modality. In this review, we summarize recently published data on the efficacy of endoscope guided interventional procedures with radioactive seeds. Firstly, EUS-guided iodine-125 seed implantation was reported to have a short-term efficacy on pancreatic cancer, with a three-month partial remission rate of 13.6% to 27%. Thereafter, feasibility of celiac ganglion radiation was tested in animal models to achieve pain relief. Recently, a seed-based stent has been introduced in the endoscopic retrograde cholangio-pancreatography (ERCP) drainage of biliary obstruction caused by pancreatic cancer, with a response rate of 72.7%. In addition, we discuss the potential of radioactive seed-based, endoscope-assisted interventional treatment of patients with locally advanced pancreatic cancer. Further studies should focus on the precise amount and distribution of seeds with the aim to improve the survival rate as well as the quality of life.