The performance of polymer electrolyte membrane fuel cells (PEMFCs) is greatly influenced by the residual water content generated during the cell operation. A comprehensive understanding of water management at the interfacial regions of PEMFC components is critical for elevating the efficiency of PEMFCs. Herein, the liquid transport and accumulation at the interfacial region of 2D microporous layer (MPL) and catalyst layer (CL) are investigated numerically, considering the effects of compression stress, porosity, and wettability. The numerical scheme is assembled by finite element method (for interfacial contact mechanics) and lattice Boltzmann method (for multiphase flow and permeability calculation). Different levels of compression stress derived from fuel cell assembly pressure are applied on the MPL/CL components, which consequently lead to variations in the pore size distribution and porosity change of the MPL/CL. The results highlight the importance of considering porosity change in the compression process, where increasing compression stress significantly decreases the liquid saturation in the MPL and interfacial gap region. Additionally, strong hydrophobicity can alleviate the heterogeneity of liquid accumulation at the MPL/CL interfacial region. The liquid and gas relative permeability are also investigated to assess the liquid drainage and fuel supply efficiency with different compression stress.