Regulating the rational wettability on gas-diffusion electrodes (GDEs) plays a pivotal role to improve the efficiency of CO2RR via fine-tuning the reaction zone and boosting the formation of triple-phase interfaces. Herein, we present a wettability regulation strategy that modulates the triple-phase reaction zone in the catalyst layer of GDEs. This strategy was employed on a flow-through hollow fiber GDE coated with a Bi-embedded catalyst layer. Compared to other ex-situ methods (e.g., adding wetting agents) affecting the bulk of electrocatalysts or catalyst layer, we create distinctive hydrophilic-hydrophobic regions within the catalyst layer. Catalyst layer with hydrophilic-hydrophobic regions outperforms the fully hydrophilic one by facilitating the species transport, boosting triple-phase interface formation, and maximizing the active sites. This regulation strategy showed stable wettability during CO2RR cathodic conditions, evidenced by the direct measurement of penetration depth. The electrode with the regulated wettability exhibited over 80% catalyst utilization and 4 times higher formate partial current density (~150 mA cm−2 with FEformate> 90%) compared to the untreated electrode, outperforming other GDEs employed for CO2RR to formate in the same concentrations of bicarbonate. The finding of this versatile microenvironment regulation strategy can be extended to GDEs used for other gas-phase reactions.@en