The burst release of drug molecules from natural biopolymer-based hydrogels is a common issue in the field of controlled drug delivery systems. pH- and magnetism-responsive sodium alginate/Fe₃O₄@HNTs nanocomposite beads for controlled release of granulysin were prepared. Fe₃O₄@HNTs were prepared by growth of Fe₃O₄ nanoparticles on the surface of HNTs via solvothermal reactions. Then, the SA/Fe₃O₄@HNTs-granulysin nanocomposite beads were prepared by sol–gel transition of the SA-granulysin aqueous solution with homogeneously dispersed Fe₃O₄@HNTs. The nanocomposite beads were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. In addition, the factors, e.g., the concentration of SA, weight ratio of Fe₃O₄@HNTs to SA and weight ratio of FeCl₃·6H₂O to HNTs, influencing granulysin loading and controlled release behavior were systematically studied. The entrapment efficiency was enhanced to 61.4% and the burst release of granulysin was overcome by introducing appropriate amounts of HNTs and the Fe₃O₄ nanoparticles. Granulysin was released at a steady rate in pH 7.4 PB owing to the synergistic effects of SA, HNTs and the Fe₃O₄ nanoparticles. The release kinetics of granulysin from the nanocomposite beads follows the Higuchi model. HNTs and the Fe₃O₄ nanoparticles formed additional crosslinkages in the nanocomposite beads, which changed the swelling behaviors of the beads, and then improved the controlled release behaviors of the model drug molecules.