Abstract: Radiotherapy is one of the main methods of tumor therapy. The radiosensitivity of tumor is closely related to inhibitor of apoptosis proteins(IAPs)and the second mitochondria-derived activator of Caspase(Smac). IAPs can inhibit apoptosis by binding and inhibiting Caspase-3, 7, 9. High expression of IAPs has been shown to interfere with the efficacy of radiotherapy. Smac, upon apoptotic stimuli, is released into the cytoplasm to inhibit the caspase-binding activity of IAPs. Therapies targeting of IAP proteins may show new perspectives to overcome radioresistance. In vitro and in vivo preclinical studies have demonstrated that the combination approach warranted further clinical investigation. Thus, combination protocols using IAPs antagonists together with radiotherapy may pave the avenue to more effective radiation-based treatment options for tumor patients.