This paper addresses the application of genetic programming (GP) to the synthesis of multicomponent products nonsharp distillation sequences, and the proposed method regards minimizing the annual total cost as an optimization objective and seeks the nonsharp separation optimal flow to give the major technological parameters of the important equipment which provide the accurate theoretical basis for actual production. In combination with the domain knowledge of chemical engineering, some evolutionary factors are improved, and a set of a special encoding method and solving strategy is proposed to deal with this kind of problem. The system structural variable is optimized by GP, and the continuous variable is optimized by the complex algorithm simultaneously. Because GP has the automatic searching function, the optimal solution can be automatically found including distillation, splitting, blending, and bypassing operations without any superstructures of nonsharp distillation sequences. Three illustrating examples are presented to demonstrate the effective computational strategies.