Mechanical properties, such as strength and stiffness, of laminated carbon fiber reinforced plastic (CFRP) are generally affected by the lay-up method. However, no precise design rules to replace steel products with CFRP have been established that satisfy these properties. Therefore, this study proposes a set of rules to design automotive parts with equivalent bending stiffness through structural analysis and genetic algorithms (GAs). First, the thickness of the CFRP product was determined by comparing the bending deformation of steel products by structural analysis. To minimize the orthotropic characteristics of CFRP, the quasi-isotropic lay-up method was implemented to determine the thickness. Next, the lay-up angle was determined using GAs. The optimized lay-up angle of the CFRP product with minimum bending deformation was determined by population generation, cross-over, mutation, and fitness evaluation. CFRP B-pillar reinforcement was fabricated using the determined conditions and the bending deformation of the single component was evaluated. Finally, the B-pillar assembled with CFRP reinforcement was investigated by the drop tower test.