Poor water solubility as well as poor bioavailability of curcumin has greatly hindered its applications in cancer therapy. In the present study, a highly water soluble curcumin nano-formulation was developed and its in vivo anti-cancer efficiency in nude BALB/c mouse model was evaluated. Unlike native curcumin, the developed curcumin micelles were quickly dissolved into aqueous solution with significant improvement of water solubility (-10(4) fold increasement compared to its native form). The developed curcumin micelles had a narrow size distribution (18-28 nm) with high drug encapsulation efficiency (85%-95%). The developed curcumin micelles were characterized by X-raydiffraction (XRD), Differential scanning calorimetric (DSC), and Fluorescence spectral analysis. We observed the enhanced stability of curcumin in micelles formulation in phosphate buffer solution (PBS). In vitro cytotoxicity assay indicated that the curcumin micelles was comparatively more effective than native curcumin against various cancer cell lines due to the enhanced cellular uptake of curcumin yet resulting in the apoptosis of cancer cells. Western blotting study revealed that the induction apoptosis of S-65 cancer cells by curcumin micelles was mainly due to the down-regulation of p-Rb, Blc-2, p-AKT expression and caspase-9 activation. In vivo anti-tumor test in nude BALB/c mouse bearing S-65 xenografts indicated the intraperitoneal injection of curcumin micelles (25 mg/kg) could significantly inhibit tumor growth as compared with native curcumin treatment (p < 0.05), which was accompanied by significantly increased apoptosis of tumor cells and diminished vascular endothelial growth factor expression in tumor tissue (p < 0.05).