Based on a typical masonry structure project, the number of structural floors and mortar strength are taken as control variables, and three reinforcement schemes are used to perform variable parameter modeling calculations, which results in the difference of comprehensive seismic capacity indices of floors and reinforcement costs of variable parameter models, and establishes a masonry structure reinforcement cost-effectiveness ratio model. According to the established masonry structural reinforcement cost-effectiveness ratio model, considering the economic, technological, functional, and effectiveness impacts of the reinforcement program in an integrated manner, combined with the combined assignment-TOPSIS algorithm, a set of masonry structural seismic reinforcement optimization methods based on cost-effectiveness ratio is established. The results show that the proposed optimization method can better combine quantitative and qualitative indicators to give the optimal reinforcement scheme in a scientific and reasonable way.