Copper Cysteamine (Cu-Cy) is a new photosensitizer and a novel radiosensitizer that can be activated by light, X-ray and microwave to produce singlet oxygen for cancer treatment. However, the killing mechanism of Cu-Cy nanoparticles on cancer cells is not clear yet and Cu-Cy nanoparticles as novel radiosensitizers have never been tested on colorectal cancers. Here, for the first time, we investigate the treatment efficiency of Cu-Cy nanoparticles on SW620 colorectal cells and elucidate the underlying mechanisms of the effects. The results show that X-ray activated Cu-Cy nanoparticles may kill SW620 cancerscells is in a dose-dependent manner. The JC-1 staining shows the mitochondrial membrane potential is decreased after the treatment. The observations confirm that Cu-Cy nanoparticles may improve X-ray radiotherapy on cancer treatment and X-ray activated Cu-Cy nanoparticles can be efficiently destroy colorectal cancer cells by inducing apoptosis as well as autophagy. As a new type of radiosensitizers and photosensitizers, Cu-Cy nanoparticles have a good potential for colorectal cancer treatment and the discovery of autophagy induced by X-ray irradiated Cu-Cy nanoparticles sheds a good insight to the mechanism of Cu-Cy for cancer treatment as a new radiosensitizers.