Worldwide, a number of research groups are functioning towards effective treatment of colon cancer using chemotherapeutic agents. Nonsteroidal anti-inflammatory drugs are among the most potent agents discovered for the inhibition of cancer. In spite of the approval of celecoxib for adjuvant therapy in patients with familial adenomatous polyposis and precancerous disease of colon, associations of larger intensity of side effects limit its usage in cancer therapy. Combination therapy provides advantages of reduction in dose and possible reduction in toxicity and acquired drug resistance. As a consequence, targeted drug delivery and targeted molecular therapy of single or combination of anticancer agents are necessary for efficient treatment of colon cancer with reduced toxicity. In our study, combination of celecoxib and AEE788 shows growth inhibition and apoptosis in HCT 15 cells. Further, nanocarrier mediated celecoxib delivery showed high entrapment efficiency, sustained release patterns, desirable hemocompatibility and enhanced cytotoxicity and apoptosis in vitro and in vivo.