As a new type of machine, field vegetable power machinery can realize different pre-harvest mechanization operations. The frame is subjected to various loads during field operations, which is accompanied by dynamic load. It is necessary to carry out strength research and optimization design of the frame. The multi-objective topology optimization design method based on field measured strain data was studied. HyperWorks software was used to carry out finite element analysis of the frame, the stress distribution under static stress analysis conditions was obtained, and the fatigue damage hotspot of the frame was determined. On the basis of data analysis, the strain gauges were pasted, and the dynamic strain test system was set up to collect the load time history under typical working conditions of field vegetable power machinery. The measured strain time history data was preprocessed, and the force of the frame under the corresponding working conditions was analyzed. The load spectrum was compiled by nCode software, and the fatigue analysis and life prediction of the frame were performed. Based on the analysis and life prediction, the topology optimization was proposed, and a multi-objective topology optimization mathematical model with multiple frame conditions and dynamic low-order natural frequency response was constructed to carry out lightweight design. The test results showed that the fatigue life at the cross weld of the frame was 7.5×104 h, the fatigue life was the shortest among the 15 points, which met the service life requirement, and the overall structural strength of the frame was over-designed. The optimized frame quality was reduced by 443.55 kg, which was reduced by 53.47%.