Our previous work proved that the thermal stability of Candida rugosa lipase (CRL) immobilized on zwitterionic polymer (poly(carboxybetaine methacrylate)) grafted silica nanoparticle (SNP) was much higher than that on poly(glycidyl methecrylate) (pGMA) grafted SNP, while the latter showed significantly increased activity. Inspired by the research, we have herein proposed to synthesize copolymers of zwitterionic sulfobetaine meth-acrylate (SBMA) and GMA for CRL immobilization. The copolymers were grafted onto SNP surface at three GMA/SBMA (G/S) molar ratios (G100/S0, G50/S50, G10/S90), followed by the covalent coupling of CRL to the surface copolymers. The immobilized CRLs on the corresponding supports were denoted as p(G100-S0)-CRL, p(G50-S50)-CRL and p(G10-S90)-CRL. The enzyme loading increased with the increase of GMA content in the copoly-mer, while the activity varied with the grafted copolymer composition. Kinetic study proved the improvement of enzyme-substrate affinity after immobilization. In comparison to p(G100-S0)-CRL, p(G50-S50)-CRL and p (G10-S90)-CRL presented remarkably enhanced thermal stability and pH tolerance, and p(G10-S90)-CRL showed the highest stability. These results suggest that the copolymer design is promising for development as a versatile platform for enzyme immobilization.