The flexural deformation of printing cylinder under the printing pressure is an important factor influencing printing quality. Structural design method of printing cylinder based on topology optimization and size optimization was put forward with an example of PZ1740 blanket cylinder. In topology optimization, two-dimensional topological model was established; the topology distribution was obtained with minimizing compliance as objective and volume fraction as constraint. Parametric model of printing cylinder was built for size optimization; detailed structure of printing cylinder was obtained using minimizing flexural displacement objective and mass as constraint. The optimization results showed that printing cylinder structure can effectively reduce flexural displacement under constraint mass; the proposed method is feasible and effective for optimal design of offset printing cylinder.