In this study, a drug delivery system for chemo-hyperthermia applications is proposed and fabricated. The delivery system consists of magnetic-silica (MagSi) particles being encapsulated within a pH/thermo-responsive chitosan‑g‑N‑isopropylacrylamide (Chi-g-NIPAAm) polymer matrix. The as-prepared MagSi@Chi-g-NIPAAm particles exhibit superparamagnetic behavior with a saturation magnetization (Ms) of 20.14 emu/g. In addition, the MagSi@Chi-g-NIPAAm particles can act as a heat source when subject to an alternating magnetic field (AMF) and have a specific absorptions rate (SAR) of 8.36 Wg. The release of the drug DOX from the synthesized particles is sensitive to both the pH and temperature of its environment. We have compared the drug release when the solution is externally heated up and when it is heated up by the AMF (internal heating). For external heating (when the pH/temperature is 4.0/45 °C), 83.30 ± 2.92% of the DOX were released within the first 5 h. The release of the DOX by the particles in pH 7.4 (temperature of 37 °C) was much slower (around 25.87 ± 1.30% after 25 h). The release of the DOX was much higher (under an acidic condition pH = 4.0) around 57.13 ± 2.36% within 1 h in the presence of AMF heating. The in vitro cytotoxicity tests of the of DOX-loaded MagSi@Chi-g-NIPAAm particles towards HeLa cancer cells. In general, the toxicities of the drug DOX as part of a MagSi@Chi-g-NIPAAm particles were less than those of the standalone DOX until the concentration of DOX-loaded particles reached 250 μg/mL, after which the toxicity of DOX in both forms were the same.