Abstract: In order to prepare nanoparticles for inclusion of hesperidin (HP), the pH-driven method was used in this study to prepare zein (ZE)-sodium caseinate (SC)-fucoidan (FD) ternary composite nanoparticle, and its preparation conditions were optimized. The interactions between ZE, SC, FD and HP were investigated by Fourier transform infrared spectroscopy (FTIR), and the micromorphology of the nanoparticles was observed by scanning electron microscopy (SEM). The pH stability and ion stability of the nanoparticles were also studied. The results showed that the optimum mass ratio of Zein-SC-FD was 1:1:1. The average particle size of HP-ZE-SC-FD nanoparticles loaded with HP was 101.8±0.7 nm, its zeta potential was −36.1±1.0 mV, and the encapsulation efficiency of HP was 84.35%. The results of FTIR showed that the main forces between ZE, SC, FD and HP included hydrogen bonding, electrostatic and hydrophobic interactions. The SEM results showed that the microstructure of HP-ZE-SC-FD nanoparticles was spherical or ellipsoidal. HP-ZE-SC-FD nanoparticles showed good stability in the range of pH2.0~8.0 and NaCl concentration 0~3.0 mol/L. This study shows that ZE-SC-FD nanoparticles are a good carrier for encapsulating and protecting HP, which can provide a theoretical basis for the research and development of functional foods or health products containing HP.