Anion-exchange membrane fuel cells hold promise to greatly reduce cost by employing nonprecious metal cathode catalysts. More efficient anode catalysts are needed, however, to improve the sluggish hydrogen oxidation reaction in alkaline electrolytes. We report that BCC-phased PdCu alloy nanoparticles, synthesized via a wet-chemistry method with a critical thermal treatment, exhibit up to 20-fold HOR improvement in both mass and specific activities, compared with the FCC-phased PdCu counterparts. HOR activity of the BCC-phased PdCu is 4 times or 2 times that of Pd/C or Pt/C, respectively, in the same alkaline electrolyte. In situ HE-XRD measurements reveal that the transformation of PdCu crystalline structure favors, at low annealing temperature (<300 °C), the formation of FCC structure. At higher annealing temperatures (300-500 °C), a BCC structure dominates the PdCu NPs. Density functional theory (DFT) computations unravel a similar H binding strength and a much stronger OH binding of the PdCu BCC surface (cf. FCC surface), both of which are simultaneously close to those of Pt surfaces. The synergistic optimization of both H and OH binding strengths is responsible for the enhancement of HOR activity on BCC-phased PdCu, which could serve as an efficient anode catalyst for anion-exchange membrane fuel cells. This work might open a new route to develop efficient HOR catalysts from the perspective of crystalline structure transformation.