The global burden of cancer have encouraged oncologists to develop novel strategies for treatment. Present study was proposed to develop Arginyl-glycyl-aspartic acid (RGD)-containing nanostructured lipid carriers (NLC) as a delivery system for improving the anticancer capability of epigallocatechin gallate (EGCG) on breast cancer cell line by attaching to integrin superfamily on cancer cells. For this purpose, RGD-containing EGCG-loaded NLC were prepared by hot homogenization technique and characterized by different techniques. Then, cytotoxic and apoptotic effects of prepared nanoparticles and their uptake into cells was evaluated. As results, the nanoparticles with particle size of 85 nm, zeta potential of −21 mV, encapsulation of 83% were prepared. Cytotoxicity and apoptosis experiments demonstrated that EGCG-loaded NLC-RGD possessed greatest apoptotic activity. Furthermore, it has been shown that, EGCG-loaded NLC-RGD causes cell cycle arresting more effective than EGCG. Therefore, loading EGCG into NLC-RGD make it more effective in both targeting and accumulation into tumour cells, which results from specialized uptake mechanism by adhesion to αvβ3 integrin. The results strengthen our hope that loading EGCG into RGD-containing NLC could possibly overcome the therapeutic limitations of EGCG and make it more effective in cancer therapy.