Background: limitation of curcumin use as antioxidant and anticancer may related to its low bioavailability so its use as nanocurcumin may improve its effect.  Aim: this study was designed to investigate the possible chemoprotective and cytotoxic effect of nanocurcumin against Human colorectal carcinoma (HCT-116) cell line  Material and methods: MTT assay was performed to detect the cytotoxic effect of nanocurcumin against normal and HCT-116 cells, and determination of gene expression of P53, BAX, Caspase-9 and BCL-2 was performed to detect the apoptotic effect of nanocurcumin  Results: nanocurcumin has a selective cytotoxic effect on human HCT-116 cells with no cytotoxic effect on healthy cells. At the same time, nanocurcumin increases the expression of P53, BAX and Caspase-9 with reduction in expression of BCL-2 gene in medium and high doses with no effect in lower dose  Conclusion: nanocurcumin has selective cytotoxic and chemoprotective effect against human HCT-116 cells according to its dose used.