In this study, we investigated in detail the crosstalk between selenite-induced autophagy and apoptosis in colorectal cancer cells and elucidated the role of ROS/AMPK/FoxO3a/GABARAPL-1 signaling pathway in regulating protective autophagy over apoptosis in both colorectal cancer cell lines and xenograft tumor model. The gene discussed is FOXO3; the disease is colorectal cancer.