Electrochemical catalysis of carbon-based material via two-electron pathway oxygen reduction reaction (ORR) offers great potential for in-situ hydrogen peroxide (H2O2) production. In this work, we tuned catalyst mesostructure and hydrophilicity/ hydrophobicity by adjusting polytetrafluoroethylene (PTFE) content in graphite/carbon black/PTFE hybrid catalyst layer (CL), aimed to improving the 2-electron ORR activity for efficient H2O2 generation. As the only superhydrophobic CL with initiating contact angles of 141.11 °, PTFE0.57 obtained the highest H2O2 yield of 3005 ± 58 mg L-1 h-1 (at 25 mA cm-2) and highest current efficiency (CE) of 84% (at 20 mA cm-2). Rotating ring disk electrode (RRDE) results demonstrated that less PTFE content in CLs would result in less electrons transferred and better selectivity towards 2-electron ORR. Though the highest H2 concentration (2 mg L-1 at 25 mA cm-2) was monitored from PTFE0.57 which contained the lowest PTFE, the CE decreased inversely with increase of PTFE, which proved that H2O2 decomposition reaction was the major side reaction. Higher PTFE content increased the hydrophilicity of CL for excessive H+ and insufficient O2 diffusion, which induced H2O2 decomposition into H2O. Simultaneously, electroactive surface area of CLs decreased with higher PTFE content, from 0.0041 m2 g-1 of PTFE0.57 to 0.0019 m2 g-1 of PTFE4.56. Besides, higher PTFE content in CL leads to the increase of total impedance (from 14.5 Ω of PTFE0.57 to 18.3 Ω of PTFE4.56), which hinders the electron transfer and ORR activity furtherly.