The structural stability of antibody protein etanercept was studied in different protective systems, including the vacuum freeze-drying and aqueous solution environment, by using the molecular dynamics simulation method with Gromacs software. Through analyzing the structural changes of etanercept as well as the intermolecular interaction between etanercept and protectants, the significant difference between various protective systems and antibody protein was analyzed by one-factor analysis of variance. The results show that the stabilizing effect of both trehalose-mannitol complex protective system and the sucrose-mannitol complex system on antibody protein is better than that of the single trehalose system, and the trehalose-mannitol complex protective system is most effective to preserve the bioactive structure of etanercept.This indicates that the small molecule protectants can synergistically protect the bioactive structure of antibody proteins, and the solvent environment has a significant effect on the stability of antibody proteins, while the vacuum freeze-drying can improve the stability of their bioactive structure.