Aiming at the runner design feature of injection mold of combinational cavities laid in non-natural balance, the design method of multi-objective runner optimization is put forward based on Kriging model. At fist, the basic theory of Kriging approximate model is proposed, and aiming at the feature of combinational cavities, the multi-objective optimum model of runner system is proposed also. In the solving multi-objective optimum model, the multi-objective ant colonies algorithm with crossover and mutation based on Pareto optimization is proposed. The given method is testified by a runner design instance of top and down cover of mouse, and it has a good application in engineering. The optimum result shows that the multi-objective ant colonies algorithm with crossover and mutation has good algorithmic performance.