To improve the cross-linking efficiency of gelatin molecules, sodium acetate trihydrate/urea deep eutectic solvent with 30% water (SAT/U-DES30W, based on DES weight) was proposed as the solvent of gelatin in this paper. The system could overcome the gelation effect of gelatin at low temperature and expose more active groups of gelatin molecules, resulting in better cross-linking effect. Firstly, the optimal reaction concentration of epichlorohydrin (ECH) was determined by boiling water solubility of cross-linking products, and the cross-linking efficiency of gelatin under two systems was judged together with the Glass transition temperature method. Secondly, the water resistance of the cross-linked product was investigated by swelling capacity and water contact angle. The water absorption rate of GE(W) and GE(DES) decreased from 4614% to 1500% and 929% at 12 h, respectively, and the water contact angle also obviously decreased, indicating that the cross-linking efficiency of gelatin under DES system was higher. Finally, the cross-linking mechanism of gelatin and ECH were discussed and it was found the thermal stability of GE(DES) was significantly improved, which would provide a theoretical basis for gelatin-based materials.