To improve the structural strength of internal combustion engine crankshaft, the response surface model of crankshaft structural strength was established and corrected by using least square method, significance analysis and fitting accuracy test based on the finite element simulation of whole crankshaft in real operating conditions of internal combustion engine. Sampling was conducted through the central composite design test method. The response surface model was optimized by using the combination of simulated annealing and direct HookeJeeve search algorithm while certain key structural dimensions of crankshaft were taken as the design variables. Optimization of a certain internal combustion engine crankshaft was carried out. The results showed that the proposed method could greatly improve the optimization efficiency of crankshaft design and as well had high accuracy.