The work aims to optimize the structure of the variable-stiffness printing cylinder to effectively improve its resistance to axial deflection deformation and improve the uneven distribution of printing pressure. According to the radial load distribution theory of bearing, the equivalent support model of variable-stiffness printing cylinder was established. The finite element analysis of the axial deflection deformation of the variable-stiffness printing cylinder was used to select the factors that have great influence on the deflection deformation. The experimental group of variable-stiffness printing cylinder structural distribution and structural size was established by the orthogonal test method. Extremum difference analysis was carried out to judge the maximum deflection deformation of the variable-stiffness printing cylinder as the evaluation index, and analyze influences of various factors on the axial deflection deformation. The degree of primary and secondary and the law of influence were analyzed to obtain a better structural distribution and structural size. The results showed that the thickness of the cylinder and the number of ribs had greater influences on the maximum deflection deformation of the variable-stiffness printing cylinder, and the reinforcement rib thickness and the mandrel diameter were the second; after optimization, the deflection deformation of the variable-stiffness printing cylinder was improved, and the axial maximum deflection deformation was reduced by 10.2%. Reasonable improvement of the variable-stiffness printing cylinder structure can reduce its axial deflection deformation and effectively improve the quality of the printed matters.