To reduce the wear of the full-floating piston pin friction pair in a certain high-power marine diesel engine, a polynomial profile expression method with continuous curvature at the segment was proposed, and the profile of the pin hole was optimized. A sub-model for the contact area between the pin and pin hole was established based on the thermo-mechanical coupling model of the piston pin friction pair for pin hole profile optimization, which can improve computational efficiency by 120 times. A high-order curve was designed based on the foundation of the previous job to replace the original conical profile. The pin hole profile was optimized using the sub-model and a Python-driven automatic surface design method, resulting in a 12.7% reduction in the maximum stress of the pin hole. A thermo-elastic hydrodynamic lubrication model for the piston-pin-connecting rod was constructed to compare the lubrication and wear performance before and after the pin hole profile optimization. The effectiveness of the profile optimization was verified through a single-cylinder engine test.