The integration of an approximate model and a clonal selection algorithm (CSA) is considered to one of the most effective ways to solve complex optimization design problems in engineering. In this study, first, a process for developing an approximate model and the principles of clonal selection algorithms were presented. Then, a variotherm temperature injection mold used to produce a large liquid crystal display (LCD) TV panel was demonstrated and an approximate model for optimizing the layout of the heating channels in the mold was established. Third, the clonal selection algorithm program was coded according to the aforementioned principles to solve the established approximate model. Finally, the layout of the heating channels was optimized and the optimal solutions were obtained. Finite element simulation and industrial injection production indicated that the integration of the approximate model and clone selection algorithm used in this study to optimize the layout of the heating channels for the injection mold was very effective.