An explicit dynamic simulation of the vertical crash of a regional airliner’s middle fuselage section has been conducted to investigate its crashworthiness. The simulation result shows that there are two major acceleration peaks in the crashing process when the crash velocity is . The initial acceleration peak is 15.8 g, and the secondary acceleration peak is 24.2 g with a duration of 0.02 s. The crash load efficiency is only 25.8%. The structural behavior above cannot satisfy the design requirements. In this paper, the topometry optimization method is applied to the crashworthiness design of the aircraft. The crashworthiness design of the fuselage is optimized using the target force–displacement response method proposed by the authors. The results show that the optimized fuselage structure of the airliner will produce more plastic hinges to dissipate the kinetic impact energy during the crash process. Therefore, the initial acceleration peak decreased to 11.7 g (decreased by 25.7%) and the secondary acceleration peak is completely eliminated. The acceleration–time curve is smoother than the initial design, and the crash load efficiency increased to 54.1% from 25.8%.