This study investigates the enhancement of alkaline hydrogen oxidation reaction (HOR) activity and stability by implanting oxophilic metal atoms into PtRu nanowires. The researchers found that dual doping with In and Zn atoms significantly improved the mass activity and specific activity of the catalyst, outperforming commercial Pt/C and PtRu/C catalysts. The optimal catalyst, i-ZnIn-PR/C, exhibited a mass activity of 10.2 A mgPt+Ru−1 at 50 mV, which is 37.8 and 8.2 times higher than that of commercial Pt/C and PtRu/C, respectively. Additionally, i-ZnIn-PR/C demonstrated superior stability and resistance to CO-poisoning, with a current decay of only 5.3% after 10,000 s at 100 mV. In an anion exchange membrane fuel cell (AEMFC), i-ZnIn-PR/C achieved a peak power density of 1.84 W cm−2 and a specific power density of 18.4 W mgPt+Ru−1 with a low noble metal loading. Advanced experimental characterizations and theoretical calculations revealed that the introduction of In and Zn atoms optimized the binding strengths of intermediates and promoted CO oxidation, enhancing the HOR performance. This work deepens the understanding of developing novel alloy catalysts for efficient and stable hydrogen oxidation reactions.This study investigates the enhancement of alkaline hydrogen oxidation reaction (HOR) activity and stability by implanting oxophilic metal atoms into PtRu nanowires. The researchers found that dual doping with In and Zn atoms significantly improved the mass activity and specific activity of the catalyst, outperforming commercial Pt/C and PtRu/C catalysts. The optimal catalyst, i-ZnIn-PR/C, exhibited a mass activity of 10.2 A mgPt+Ru−1 at 50 mV, which is 37.8 and 8.2 times higher than that of commercial Pt/C and PtRu/C, respectively. Additionally, i-ZnIn-PR/C demonstrated superior stability and resistance to CO-poisoning, with a current decay of only 5.3% after 10,000 s at 100 mV. In an anion exchange membrane fuel cell (AEMFC), i-ZnIn-PR/C achieved a peak power density of 1.84 W cm−2 and a specific power density of 18.4 W mgPt+Ru−1 with a low noble metal loading. Advanced experimental characterizations and theoretical calculations revealed that the introduction of In and Zn atoms optimized the binding strengths of intermediates and promoted CO oxidation, enhancing the HOR performance. This work deepens the understanding of developing novel alloy catalysts for efficient and stable hydrogen oxidation reactions.