Cholangiocarcinoma (CC) is a malignant tumor originating from the epithelial cells of the bile ducts with high degree of malignancy and poor prognosis. Current treatment methods mainly include radical resection, palliative surgery, chemotherapy, and radiotherapy, but all these methods exert little impact on patients’ survival. 125I seed implantation is a recently emerging technique for cancer therapy. It has better safety and efficacy, and can effectively improve the survival of CC patients in combination with other treatment methods, but still has some disadvantages. Here, the authors present the progress of 125I seed implantation in CC treatment.