Engineering structural defects is beneficial for electrocatalytic performances. Herein, a class of acid-etched PtNiRh nanotubes with abundant structural defects around cavities were constructed. Modulated electronic and coordination structures closely associated with structural defects boost the ethanol oxidation reaction (EOR) activity and selectivity. The optimized PtNiRh-E-H nanotubes exhibit an EOR mass and specific activity of 1.81 A mgPt–1 and 3.38 mA cm–2, respectively. A high retention at 1.80 A mgPt–1 after a chronoamperometric test of 10000 s was achieved by PtNiRh-E-H nanotubes. Moreover, the PtNiRh-E-H nanotubes featuring compressive lattice strain and lower-lying d band center display a strong inclination for the C1 pathway, as evidenced by a higher linearly bonded CO band intensity and lower intensity of adsorbed acetate across the applied potentials using attenuated total-reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS). Also, the attenuated CO adsorption and accelerated CO oxidative desorption by OH species led to superior C1 selectivity of the PtNiRh-E-H nanotubes. Differential mass spectrometry (DEMS) together with ATR-SEIRAS provides explicit evidence of catalytic pathway as CH3CH2OH → CH3CH2OHads → ··· → CH3CHO → CH3CO → CH3 + CO → 2CO2. The work represents a feasible strategy for alcohol oxidation catalysis, wherein acid etching exposes significantly more structural defects and brings about an optimal electronic structure and lattice strain.