One of the main reasons for mortality in the world is cancer. In spite of present progress in cancer biology which causes better diagnose and treatment, cancer fatality is yet noticeable. This can be due to a disability to deliver the drug to the infected tissue selectively without side effects on intact organs. A great amount of drug is also degraded in intact tissue and organs which result in severe side effects. Systemic effects of anticancer drugs are mostly due to dissolubility and instability of drug in biological environments, low concentration of drug around the tumor, the low functionality of drugs toward solid tumors and undesirable effect of the drug on intact tissues. For overcoming such problems, developing target drug delivery systems, which release drugs or bioactive agents in the desired area, is of great importance. In this study, various nanofibrous formulations loaded by anticancer drug 5FU have been compared, which included chitosan/PCL blended nanofibers, chitosan/PCL/Fe 3 O 4 blended nanofibers and core-shell nanofibers loaded by magnetic nanoparticles. These formulations in comparison of other nanocariers, could be improved the release of 5FU and reduces its rapid degradation in biological environment lead to sustained and prolonged release, because of, nanofibers high drug loading efficiency and unique properties of chitosan. The magnetic iron oxide nanoparticles in these nanofibers lead to hyperthermia and drug treatment usage simultaneously could have more effective to treat cancer tumor. The results, show that increasing of chitosan amount, increases drug loading efficiency, maximum release and release time. FTIR analyzing indicates that there are not any interactions between 5Fu and other nanofibers components. Also, there are uniform dispersion of drug and iron oxide nanoparticles in nanofibers mat according to EDX analyses. Core-shell nanofibers structure is modeled by an artificial neural network (ANN). After function approximation of nanofibers structure and release parameters by ANN, the structure parameters were optimized by genetic algorithm in which GA fitness function defined based on ANN. The reproduced core-shell structure released 78% of 5FU during 144 hours. Also, the encapsulation efficiency of this nanofibrous mat was 81%. The release parameters of optimized nanofibers and estimation of ANN have been compared. The results show that, this ANN could be modeled the relation of structural parameters and release parameters with an acceptable error (10.65%). The cell cytotoxicity test showed that the optimum core-shell nanofibers can restrain HepG-2 cells and the cytotoxicity of them was 40% after 72 hours approximately. This drug delivery system is also capable of being used as postsurgical implants in cancer treatment such as liver and colorectal.