Thus, this study was designed to investigate the differential modulations of the treatments either with 5-Fu alone or 5-Fu combined with curcumin on cellular autophagic responses and viabilities in the human colon cancer cells HCT116 and HT29, and then to further explore if such autophagic responses could be attributed to curcumin-mediated changes on Akt/mTOR/ULK1 and AMPK-ULK1 signal transductions and hereby potentiate 5-Fu’s cytotoxicity in vitro and in vivo. This evidence concerns the gene AKT1 and malignant colon neoplasm.