In order to combine the advantages of a biopolymer with clay in a drug delivery system, the hot intercalation technique was used to prepare quaternized chitosan/montmorillonite (HTCC/MMT) nanocomposites. Transmission electron microscopy (TEM), x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) results revealed that HTCC chains entered into the interlayer of MMT, and the interaction between them has taken place. This is the basis of the advantage combination. Then the HTCC/MMT nanocomposites were modified to prepare the nanoparticles, whose drug-controlled release behaviours were evaluated. The results suggested that, compared to pure HTCC nanoparticles, certain montmorillonite loadings on quaternized chitosan enhanced the drug encapsulation efficiency of the nanoparticles and slowed the drug release from the nanocomposites. Finally, a study of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) indicated that the nanocomposites are not cytotoxic. Therefore, the HTCC/MMT nanocomposites are of great potential in the biomedical field.