Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer‐based pharmaceutical system together with a single‐stranded AS1411 aptamer (APTAS1411) as a therapeutic strategy. The polyamidoamine (PAMAM)‐polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic‐force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM‐PEG‐APTAS1411complex dramatically increased PAMAM‐PEG‐5‐FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle‐5‐FU‐APTAS1411 complex, by thin layer chromatography (TLC), and an increase in 5‐fluorouracil (5‐FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5‐FU to MKN45 gastric cancer cells in consistent and without toxic effects.