Although radiotherapy (RT) has been widely used for tumor treatment, it is still suffered from the following shortcomings, such as serious side effect and the limited efficacy. A novel gold nanocluster-based tumor radiodynamic therapy (RDT) has been developed and successfully applied for efficient tumor treatment. Due to the Type I radiodynamic mechanism, these gold nanoclusters can effectively kill solid tumor even under low dose X-ray irradiation and hypoxia tumor microenvironment. More importantly strong anti-tumor immune response and immune memory effect occurred during the process of RDT, which can effectively prevent potential tumor recurrence or metastasis.