In this communication, we reviewed the shear-enhanced filtration (SEF) for the separation and concentration of protein. Firstly, the configuration, operation parameter, and anti-fouling capacity for different SEF modules, including rotating disk/rotor, rotating membrane, and vibratory systems, were summarized. Then, two SEF application cases (milk solution filtration and Luzerne juice filtration) were introduced. For milk solution, milk proteins were separated and concentrated. The effects of hydraulic conditions of SEF on filtration performance were investigated by response surface methodology for process parameter optimization. Pore-blocking model was utilized for better understanding the membrane fouling mechanism. Afterwards, the retentate with high milk proteins was successfully applied for cheese production. After filtration, the membrane cleaning process was also conducted by shear effect to improve the efficiency. The other aspect, during the Luzerne juice filtration process, leaf proteins were separated and concentrated. At first, the influence of filtration module structures on filtration performance was studied. Secondly, a stepwise multisite Darcy’s law model (SMDM) was proposed to simulate the complex fouling process and calculate the key fouling parameters. At last, the operation conditions were optimized to enhance the filtration efficiency (permeate flux and filtration time) and separation performance (the protein rejection and protein purity in retentate). This work can give a valuable information for the application of SEF for the separation and concentration of protein solution.