Data reported in this study indicate that, in dead-end microfiltration of BSA solution, the compression of the deposited layer of protein aggregates on membranes governs the growth of filtration resistance in the late filtration period. Therefore, the mechanism of cake compression should be taken into account to describe the resistance growth during microfiltration. To develop a suitable model for the resistance growth due to compression, the time dependence of cake porosity was measured, and the relationship between specific cake resistance and cake porosity was determined. The results suggest that the time dependence of cake porosity can be described by the Voigt model and the relationship between porosity and specific resistance can be described by the Kozeny equation. With the Voigt model and the Kozeny equation, the resistance growth due to compression can be well modeled. By incorporating the compression model into the combined model of pore-blockage and cake-filtration, the resistance growth during microfiltration can be well described.