Abstract: The chassis frame is the installed base of the corn combine harvester, which bears a lot of force from the longitudinal bending, torsion, lateral bending, horizontal rhombic and their combined loads. The frame has obvious dynamic load characteristics, therefore the static strength check is not enough and research on the fatigue life is needed. As the lack of basic research, the key data accumulation is insufficient, the tradition design method is relatively limited, many Chinese products lack the necessary fatigue strength in design, and the reliability is poor. Experience in the automotive industry has proved that the combination of fatigue load spectrum and CAE technology can greatly improve the forecasting ability. Fatigue strength study of the corn combine harvester is the foundation of improving the reliability and an important method to reduce the structural mass. In order to reduce the structural weight and improve the fatigue reliability of the corn combine harvester, this paper studies a method to evaluate fatigue life of the main frame. Firstly, using ANSYS software, the stress distribution of the corn harvester chassis frame was analyzed, and the stress distribution of the maximum modal deformation position and under static stress analysis was obtained by the finite element analysis. The resonance was the biggest at 81.4 Hz frequency, so S8 point of the maximum strain region was placed on the frame to measure the strain. S5, S9 and S10 points were the high stress concentrated points and strain gauge needed to be placed. Other measuring point was placed on the part redesigned. Secondly, the stress data acquisition system was established, including sensors, data acquisition module and computer. Based on the modal analysis and static analysis, the strain gauge was pasted on the high stress concentrated points with the appropriate method, and the strain time histories of various typical conditions were measured through many experiments, which the operating speed of the corn harvester was the first and second gear in field operations, and the third in the road transport. Eventually, the stress and dynamic load characteristics were analyzed, the fatigue life of main frame was evaluated, and the lightweight design was completed by using nCode software. After the strain data acquisition, data preprocessing was carried out to ensure the evaluating accuracy, including the elimination of singular points, the elimination of temperature drift, noise filtering and so on. After eliminating the false data, the load spectrum was compiled by the rain flow method, and the load distribution curve of the load was obtained. Fatigue life of S-N curve was the cyclic number of fatigue crack under the condition of equal amplitude stress, and it could be considered as a superposition of different frequency and amplitude, so we used the principle of fatigue cumulative damage to evaluate the fatigue life. The result showed that, the fatigue life of the main frame was 241 000 hours. The fatigue life on the road was longer than on the field, and the fatigue life was quite different at different measuring point. The main design part was an important supporting part connecting the body and rear axle. In the fatigue life analysis, it was found that the fatigue life of part was far greater than that of the body. Based on the fatigue life distribution, the optimization design of the main part in frame was completed. The result showed the new model can reduce 24% part mass under the condition of meeting the strength requirement. In this paper, the fatigue life of main frame was studied by combining fatigue load spectrum and CAE analysis, and lightweight designed was finished. This method can not only improve the stress distribution, strengthening rigidity, but also reduce the structural weight.