In process of genechip probe design for Pathogenic microorganism detection, the selection of SNP combination is of great importance. At present, no automatic design method is reported. This work is not easy and the result is not always satisfactory. A new approach of selecting SNP combination is proposed in this paper. Genetic algorithm is used to search optimal solution on the basis of classification ability of SNP combination, which is evaluated by the rough set theory. Other related experimental parameters are also been incorporated. Experiment results show that the method can get the best SNP combination pattern efficiently and accurately, which promises it a reliable approach for the genechip probe design.