The rotating packed bed (RPB) reactor with a lab-scale mesh-pin rotor (MPR) displays the great potential for the chemical processes with viscosity reactants or solid products. However, the scale-up research of the RPB reactor with MPR needs to be taken into consideration, which is the foundation for pilot-scale and industrial application. In this work, the scale-up principles of MPR were proposed for the first time, and the hydrodynamic study was conducted by using a high-speed camera. The liquid flow patterns, impaction-disintegration modes of the droplet with the pin, and droplet diameter and velocity in different zones were investigated. The droplet diameter correlations of different zones were fitted, and the experimental measurements were effectively predicted by the correlations with deviations generally within +/- 10%. A semiempirical model of droplet velocity was established and validated. The hydrodynamic results were employed to optimize the mass transfer model and illustrate the antiblockage mechanism of the RPB reactor with scale-up MPR.