Herein, the zwitterionic material poly (carboxybetaine acrylamide) was grafted onto iron oxide to obtain biocompatible magnetic nanoparticles Fe3O4-pCBAA which were employed to immobilize enzymes. The nanocomplxes Fe3O4-pCBAA were characterized using scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential, Fourier transform-infrared (FT-IR) spectra and energy dispersive X-ray spectrometry (EDX). The urease as a model enzyme was immobilized with the novel supports and the properties of immobilized urease were further investigated in comparison with the free urease counterpart. The immobilized urease exhibited excellent thermodynamic and chemical stability. Particularly, 60% of initial activity was remained after being stored at 70 °C for 2 h while the free urease only remained 30%. Besides, the relative activity of immobilized enzyme was 1.7 times that of free ones after disposed in ethanol and 2-propanol for 2 h, and 7 times in DMF. Moreover, immobilized urease retained >80% of its initial activity after 5 cycles. In addition, the immobilization carrier Fe3O4-pCBAA displayed famous biocompatibility, and the immobilized urease performed better in complex biological samples, which were >85% and <60% of its initial activity for the immobilized and dissociative urease, respectively, in 20% and 25% of serum. These results confirm that the nanoparticles Fe3O4-pCBAA are biofriendly and efficient supports for enzyme immobilization and potential for practical applications in bio-microenvironments.