The working quality of a cotton stripper harvester is limited by the efficiency of onboard seed cotton cleaners. As a basis for research in the design of a cotton stripper harvester prototype, the bench cleaning tests were designed to study the effect of structural and technological parameters on the loss rate and impurities rate of the cleaner. According to the features of different test factors, a combined orthogonal test was applied to determine the best combination of the sawtooth distance, saw cylinder diameter, and cleaning distance. With these parameters fixed, the optimal parameters for the cleaning distance, saw cylinder rotating speed, and brush thickness were obtained using a quadratic-regression rotatable orthogonal test. The best parameter configuration to ensure the cleaning quality of the onboard seed cotton pre-cleaner included the following structural parameters: sawtooth distance of 38 mm and saw cylinder diameter of 340 mm, and technological parameters: rotating speed of 282–288 rpm, clearance of 12.55–14.84 mm, and brush thickness of 8.37–9.69 mm, which decreased the loss rate to less than 10% and the impurities rate to less than 6%. The reliability of the theoretical analysis results was verified by a comparison with experimental results. The experimental results provide a theoretical basis and technical reference for the research and the structural design of seed cotton pre-cleaners.