This study focuses on enhancing of crashworthiness and lightweight of the automotive B-pillar structure by using continuous carbon fiber reinforced thermoplastic composites (CFRTP) and optimized layer design. Firstly, the B-pillar is divided into four regions with variable stiffness. Quasi-static three-point bending test and numerical simulation are performed to calculate the stiffness of the structure. Then, the four regions of the B-pillar with different CFRTP layers are structurally designed to realize variable stiffness. Considering manufacturing requirements, a draping simulation is employed to predict potential layer defects. The results demonstrate that B-pillar structural performance is enhanced after the reorientation of CFRTP prepreg. Afterward, the crashworthiness of the CFRTP B-pillar considering the ply drop-off is evaluated and compared with the traditional Q235 steel counterparts. The results indicate that the CFRTP B-pillar exhibits superior crashworthiness but a substantial reduction in mass by 53.1 %. Finally, the multi-island genetic algorithm (MIGA) is employed to achieve the optimal layer design scheme for lay-up optimization of the CFRTP B-pillar, and the crashworthiness of the CFRTP B-pillar with variable stiffness is further improved. The current work highlights a structural design strategy for CFRTP components for vehicles, which is crucial for the updating of automobile engineering.