The gas-liquid two-phase flow is an important problem in the proton exchange membrane (PEM) electrolysis cell, however the detailed modeling is still difficult due to the complex reaction process. In this work, a comprehensive, three-dimensional, two-phase PEM electrolysis cell model is established and validated by the tested data. The electrochemical model coupled with the mass and heat transfer model is used to capture the temperature, gas fraction and current density distribution, and to explore two-phase flow effects on the cell performance. The results show that this model has a better fitting effect in the range of test current density (0–1.2A/cm2). The coverage of bubbles on the catalyst active area is the leading cause of mass transport loss. Adjusting the wettability can promote gas discharge. The combination of hydrophilic CL and hydrophobic PTL shows better performance (12.6 times the combination of hydrophilic PTL and hydrophobic CL) due to the capillary pressure. The simulation results indicate that excessive water flow will inhibit gas discharge, resulting in an increase of gas accumulation and a decrease of cell performance at high current density. Further, this model can be extended to the whole stack, and used to optimize the cell design and control strategy. •Comprehensive 3D two-phase PEM electrolysis cell model.•High accuracy to predict polarization curve than traditional single-phase model.•Mass transport loss caused by bubble coverage of catalyst active sites.•Adjusting the wettability combination of PTL and CL to promote the gas discharge.•Explanation for the role of anode water flow rate on cell performance.