In view of the multi-objective optimization design of the squirrel cage fan for the range hood, a blade parameterization method based on the quadratic non-uniform B-spline (NUBS) determined by four control points was proposed to control the outlet angle, chord length and maximum camber of the blade. Morris-Mitchell criteria were used to obtain the optimal Latin hypercube sample based on the evolutionary operation, and different subsets of sample numbers were created to study the influence of sample numbers on the multi-objective optimization results. The Kriging model, which can accurately reflect the response relationship between design variables and optimization objectives, was established. The second-generation Non-dominated Sorting Genetic algorithm (NSGA-II) was used to optimize the volume flow rate at the best efficiency point (BEP) and the maximum volume flow rate point (MVP). The results show that the design parameters corresponding to the optimization results under different sample numbers are not the same, and the fluctuation range of the optimal design parameters is related to the influence of the design parameters on the optimization objectives. Compared with the prototype, the optimized impeller increases the radial velocity of the impeller outlet, reduces the flow loss in the volute, and increases the diffusion capacity, which improves the volume flow rate, and efficiency of the range hood system under multiple working conditions.