The performance of the centrifugal fan in the pneumatic conveying system of the cotton picker has an important impact on its work, so it is of great significance to improve the working efficiency and performance of the centrifugal fan of the cotton picker. The mid-arc line of the prototype centrifugal fan blade was extracted, and the NACA 6410 airfoil with excellent flow characteristics was transplanted and coupled to the mid-arc line of the prototype blade to design a type of centrifugal fan blade. Combined with test data of prototype fan in centrifugal fan of pneumatic conveying system of cotton picker, the performance change of the fan was analyzed by CFD numerical calculation. Through the centrifugal fan performance test, the aerodynamic performance of the prototype fan and the optimized fan at different speeds was compared, and the improvement effect of new fan and influence of speed on the performance of optimized fan were discussed. The results showed that the optimized blade had good aerodynamic performance. The blade structure effectively suppressed the airflow disorder, ‘jet-wake’, flow separation and other phenomena inside the fan, making the airflow on the surface of the fan blade more stable, thereby improving the efficiency of the fan. Under the rated operating conditions, compared with the efficiency of 54.2% of the prototype fan, the efficiency of the optimized centrifugal fan was significantly improved, reaching 58.4%. This improvement showed that the performance of the fan was significantly optimized and enhanced. Compared with the prototype fan, the operating efficiency of the optimized fan at different operating conditions was improved by 3.0~5.3 percentage points. Especially at 4200r/min, the improvement of the aerodynamic performance of the fan was the most significant, and the efficiency improvement was up to 5.3 percentage points.