This work delineates the first attempt to tune the product distribution between methanol and ethanol in the direct oxidation of methane reaction by incorporating Lewis acids Ni2+, Co2+/3+or Zn2+into IrO2/CuO. The electrophilicity of Ir4+and the (LAS-BAS)/LAS ratio (LAS: Lewis acid sites, BAS: Brønsted acid sites) are demonstrated to be two reactivity descriptors motivating CH4activation and ethanol formation, respectively. Electron-deficient Ir4+motivates enriched *CH3concentration and subsequent C-C coupling for C2H4formation, while the Lewis acid promotes ethanol formation from C2H4involving lattice O and H2O. The ethanol selectivity presents a quasi-linear relationship with (LAS-BAS)/LAS. © The Royal Society of Chemistry 2021.