The efficient solid-liquid separation of fine-particle slurries is a significant challenge in mineral processing. In this study, the influence of centrifugal flow conditions and flocculation parameters on fine particle recovery was systematically investigated using cationic polyacrylamide (CPAM) and a multi-stage centrifugal cyclosizer. Static flocculation–sedimentation experiments, centrifugal classification tests, and response surface methodology were combined to evaluate recovery performance. The results showed that within a certain range, the larger the flocculant molecular weight and dosage, the better the static flocculation sedimentation performance, while appropriate centrifugal flow conditions further enhanced fine particle recovery. Response surface experiments indicated that the cyclosizer flow rate exerted the most significant influence on recovery, followed by polymer molecular weight and dosage, with a significant interaction observed between flow rate and polymer dosage. Additionally, microscopic observation and numerical simulation of the cyclosizer were combined to show a method to express the shear resistance strength of floccules using the characteristics of the flow field. In the flocculation hydrocyclone validation experiments, the addition of PAM at a dosage of 70 g/t resulted in a 2.85% increase in underflow concentration and an 8.34% improvement in yield compared with the non-PAM condition. These results indicate that centrifugal separation equipment can regulate floc stability and recovery by altering the shear rate and centrifugal force within the flow field. Therefore, achieving an appropriate balance between flow rate and flocculation intensity is essential for enhancing underflow yield.