Abstract: In this paper, the molecular simulation technique is used to study the stabilization effect of trypsin caused by hydrophilization modification. First, the tertiary structure of amine modified trypsin are built by the CVFF force field based on the crystal structure of native trypsin. The Ooi model and the Vila model are used to calculate the solvation energy of native and amine modified trypsin based on their tertiary structures. The computational results show that the solvation energy of trypsin decreases obviously after modification, with the higher degree of modification corresponding to the lower value of solvation energy. After analyzing the relationship between the solvation energy and the thermal stability in detail, it is found that the change of solvation energy can qualitatively describe the thermal stability of native and hydrophilization modified trypsin.