Abstract: Purpose To screen out the optimal conditions of cross-linking reaction of preparing for an injectable cross-linked sodium hyaluronate gel(CHA-gel) with higher resistance to hyaluronidase and research for its viscoelasticity and anti-enzyme degradation properties. Methods The CHA hydrogels were prepared with different molecular weights of PEG as cross-linking agent, such as PEG400, PEG1000, PEG6000, PEG10000, PEG20000. The optimal preparing conditions were determined by single factor test and orthogonal experiment. The Enzyme-resistant degradation properties in vitro of CHA-gels were analysed by carbazole and spectrophotometry. Its viscoelasticity was also compared with natural HA-gel by Stabinger method. Results the results of range analysis and variance analysis show that the pH of CHA solution and the ratio of cross-linking agent to HA were significant factors. The optimal preparing conditions of the parameters are 1.5% of HA, 0.001mol/L NaOH, at 37°C, reacting 4hr and 1:15 PEG20000/HA (g/g). Under these conditions, the CHA-gel has excellent Enzyme-resistant properties, R=85.1%, an high percentage of enzyme-resistant property. Its viscoelasticity can reach 61.3×104mPa.s, three times as much as natural HA-gel. Conclusion The CHA-gel with excellent physicochemical properties can be prepared under the optimal conditions, which can set foundation for developing better mechanical and Enzyme-resistant properties products of CHA-gel.