For mechanical elements running under severe working condition, there inevitably exist some small defects caused during working. The weak area, which is sensitive to defects, of the structure is more vulnerable, resulting in early damage during service. This paper describes a novel anti-defect design method for optimizing structure to enhance the reliability of vulnerable areas. First, a half-real defect model derived from the real defect is developed to model the geometrical characteristics of defects. Then, the damage degrees of model parameters are identified by Sobol’s sensitivity method and the vulnerable area can be labeled according to the damage degree. Finally, we take the vulnerable area as the object of anti-defect optimization for structure and the optimization variables are selected tendentiously based on parameters with larger damage degrees. The multiobjective particle swarm algorithm is then employed to find the optimal distribution of the variables in order to improve the safety of the sensitive area of structure. We take the impeller blade as the research subject to verify the validity of the proposed method. Analysis results showed that the proposed method can increase the structure strength and delay the damage of the mechanical elements.