In this study, a novel hydrogel, chitosan (CS) crosslinked carboxymethyl-β-cyclodextrin (CM-β-CD) polymer modified Fe3O4 magnetic nanoparticles was synthesized for delivering hydrophobic anticancer drug 5-fluorouracil (CS-CDpoly-MNPs). Carboxymethyl-β-cyclodextrin being grafted on the Fe3O4 nanoparticles (CDpoly-MNPs) contributed to an enhancement of adsorption capacities because of the inclusion abilities of its hydrophobic cavity with insoluble anticancer drugs through host-guest interactions. Experimental results indicated that the amounts of crosslinking agent and bonding times played a crucial role in determining morphology features of the hybrid nanocarriers. The nanocarriers exhibited a high loading efficiency (44.7±1.8%) with a high saturation magnetization of 43.8emu/g. UV-Vis spectroscopy results showed that anticancer drug 5-fluorouracil (5-Fu) could be successfully included into the cavities of the covalently linked CDpoly-MNPs. Moreover, the free carboxymethyl groups could enhance the bonding interactions between the covalently linked CDpoly-MNPs and anticancer drugs. In vitro release studies revealed that the release behaviors of CS-CDpoly-MNPs carriers were pH dependent and demonstrated a swelling and diffusion controlled release. A lower pH value led to swelling effect and electrostatic repulsion contributing to the protonation amine impact of NH3(+), and thus resulted in a higher release rate of 5-Fu. The mechanism of 5-Fu encapsulated into the magnetic chitosan nanoparticles was tentatively proposed.