: In recent years, researchers have been working hard to develop and control drug release systems to reduce the side effects and deliver the right dosage of the drug to the target site. The use of triggers such as temperature, electric and magnetic field, pH and light can be used as a factor in controlling its release rate. Responsive polymers for stimulants provide a good drug delivery environment that can be used to deliver drugs at a controlled time and in a stable and biologically active form. Over the past few decades, interest in responsive polymers against stimuli has grown and great work has been done to create environment-sensitive macromolecules that can become smart polymers. Smart polymers are very important in the field of drug release, tissue engineering, and medical applications that can respond to stimuli in the natural system. The smallest change in the surrounding environment causes these polymers to be responsive to the critical boundary, as well as the ability to return to the original shape after the stimulus is lost. In this research, preparation and evaluation of a layer-based nano-fiber system consisting of a mixture of poly-caprolactone/chitosan polymers containing two anti-cancer drugs, 5-fluorouracil and methotrexate, were prepared by electrospinning. In order to prepare nano-fibers, 12% w/w poly-caprolactone and 2% w/w chitosan solution were used. In order to investigate the release profile, 1% drug was added to the polymer solution and the electrospinning process was performed. Infrared spectroscopy with Fourier transform (FTIR) probabilistic drug and polymer interactions were investigated. Also, experiments were carried out to measure the release rate in phosphate buffered saline () and the concentration of the drug released in the solution was measured by the spectrophotometric method.Finally, the 3D structure of the nanofiber layers was simulated by MATLAB software, and the structure of the seven layers was constructed three-dimensionally.The results of the scanning electron microscope images showed production of beadles nanofibers. Additionally, it was found that by increasing the chitosan percentage fiber diameter decreses due to the increase in the electrical conductivity. The infrared spectra of the samples showed the presence of the drug in a polymer mixture. Also, the drug and polymer mixture did not interact with each other. The dissolution profile of the drug was studied in neutral and acidic environments for 26 days and it was observed that the drug release rate in the acidic environment is approximately two times the neutral environment.