Abstract: Seed cotton cleaning has been one of the most critical steps in cotton production and processing. Among them, the stripper-and-stick cleaner is one of the most indispensable components of the machinery during seed cotton cleaning. Its primary function is to remove the boll husks for the subsequent ginning and the ultimate high-quality lint. Specifically, the centrifugal force and the stripping action can be realized to separate the seed cotton and boll husks, where are the cleaning bars around the U-shaped saw cylinder. The existing stripper-and-stick cleaners have been designed specifically for upland cotton processing. By contrast, sea island cotton is the primary raw material for high-end textiles, with softer and finer fibers, as well as a higher coefficient of friction. Consequently, the conventional stripper-and-stick cleaners cannot fully meet the large-scale production of the sea island cotton, leading to the low cleaning rate of the boll husk, high rate of cotton loss, and serious fiber damage during cleaning. In this study, an improved stripper-and-stick cleaner was designed for the machine-harvested sea island cotton. A three-cylinder structure was also determined for the entire machine after the fiber damage analysis. The physical and mechanical properties of the machine-harvested sea island cotton were combined with the theoretical removal of the boll husk. The key structural and operational parameter ranges were also designed for the boll husk removal device and the doffing cylinder. The field experiments were carried out at a cotton processing plant in the Aksu region of Xinjiang, China, in November 2024. The test sample was taken as Xinhai 62, the machine-harvested long-staple cotton. A single-factor experiment was carried out using the seed cotton feeding speed, U-shaped saw cylinder rotation speed, and U-shaped saw cylinder and cleaning bar spacing as the control factors, with the boll husk cleaning rate and cotton loss rate as the evaluation indices. Furthermore, the seed cotton feeding speed, U-shaped saw cylinder rotation speed, and U-shaped saw cylinder and cleaning bar spacing were then determined to be in the ranges of 11-13 t/h, 170-238 r/min, and 13-19 mm, respectively. A three-factor quadratic regression orthogonal protocol was developed using the Box-Behnken design. The response surface analysis was then made on these variables using Design-Expert 13 software. The optimal parameters were obtained: the seed cotton feeding speed of 11.00 t/h, the U-shaped saw cylinder rotation speed of 219.12 r/min, and the spacing of the U-shaped saw cylinder and fiber cleaning rod of 15.61 mm. The better performance was predicted to be a boll husk cleaning rate of 64.85% and a cotton loss rate of 0.27%. The optimal parameters were rounded for the prototype test: the seed cotton feeding speed of 11.00 t/h, the U-shaped saw cylinder rotation speed of 220 r/min, and the spacing of the U-shaped saw cylinder and fiber cleaning rod of 16 mm. Experimental verification showed that the average rate of the boll husk cleaning was 64.23%, and the average cotton loss rate was 0.27% under the optimal parameters. Therefore, the improved machine achieved a 6.54 percentage point increase in the boll husk cleaning rate and a 0.81 percentage point reduction in the cotton loss rate, compared with the existing stripper-and-stick cleaner. Finally, a fiber damage test showed that the fiber length was reduced by 0.36 mm, and the fiber damage rate was 0.95% under optimal parameters in the improved machine, when processing the machine-picked sea island cotton. In contrast, the existing stripper-and-stick cleaner reduced the fiber length only by 1.02 mm and a 1.73 percentage points in the fiber damage rate. These findings can provide the technical references to update the stripper-and-stick cleaner for the machine-harvested sea island cotton.