Molecular breeding is considered an important way to improve the breeding efficiency. But due to the deletion of data, method and instrument, molecular design breeding is basically at the concept stage, without operational technology process and breeding practice. On the basis of breeding data from Beijing Kings Nower Seed S&T CO, LTD, this paper explored a set of methods for maize design breeding based on molecular detection and phenotypic testing information. Firstly, the parents of the combinations were obtained from the inbred lines with high homozygosity through SSR detecting and good comprehensive traits through field testing; secondly, the heterosis rate of the parents was got by calculating both the genetic differences and phenotypic differences of the parents according to the SSR detection results and field testing results respectively to express the special combining ability of their own; finally, in this paper it constructed the hybridization group model by using the comprehensive characters, special combining ability, orthogonal anti value, calculated the comprehensive characters, advantages, disadvantages of the hybridizations, and screened hybrid combinations to the next round field breeding, it also developed a software system of hybrid combination to support the technology route. Applying the software, 37 hybrid combinations resistance to Ralstonia solanacearum were got based on 179 inbred lines with molecular and phenotypic data. Thus, the method and software preliminary provides technical support for our country to carry out and perfect the molecular design breeding.