Chemotherapy is currently used for most cancer treatments, but one of the significant problems of this treatment is that it affects the healthy tissues of the body. Therefore, designing new systems for the intelligent and controlled release of these drugs in cancer tissues is one of the major challenges in the world. Hence, today, huge costs are spent designing appropriate new drug delivery systems (DDS) with controlled drug release. In this study, chitosan-polyacrylic acid encapsulated Fe3O4 magnetic nanogelic core-shell (Fe3O4@CS-PAA) was synthesized in the presence of glutaraldehyde used for loaded anticancer 5-fluorouracil (5-FU) drug. Also, the prepared Fe3O4@CS-PAA was characterized by using FT-IR, SEM, XRD, and VSM analysis. Then, drug delivery tests were carried out in the in-vitro conditions that are the simulated physiological environment and tumor tissue conditions. The drug release tests indicated that the Fe3O4@CS-PAA upgraded the rate of 5-FU release from nanogelic core-shell under tumor tissue conditions (pH 4.5) than physiological environments (pH 7.4). In addition, various models were used to investigate the drug release mechanism. Results of modeling studies of drug release showed the mechanism of 5-FU release from Fe3O4@CS-PAA controlled by Fickian diffusion.