To reduce the friction loss and the piston-knocking noise from the perspective of the design of the cylinder bore profile, the piston-ring cylinder bore (PRCB) dynamic model of an L6 diesel engine was developed using AVL-Excite-Piston & Rings. Based on the full-scale test method, the effects of bore taper, starting height of tapered profile, and ellipticity on the friction power and knocking energy of the PRCB system were investigated, and the optimization of the design of the bore profile was carried out with the objectives of minimizing the system’s friction power and the peak knocking kinetic energy. The results showed that the taper of the cylinder bore has the greatest influence on the system’s friction power and the peak knocking kinetic energy, followed by the starting height of the conical profile. For the peak knocking kinetic energy of the piston, there was an obvious interaction between the taper and the starting height of the conical profile. When the taper was 35 μm and 45 μm, the peak knocking kinetic energy showed a decreasing and then increasing trend with the increase in the starting height of the profile, and when the taper was 55 μm the peak knocking kinetic energy monotonically was decreased with the increase in the starting height of the conical profile. The optimization results showed that the system’s friction power was decreased by 15.05% and the peak knocking kinetic energy was decreased by 21.41% for a taper degree of 55 μm, a tapered profile starting height of 31 mm, and an ellipticity of 50 μm compared to the initial cylindrical cylinder bore.