The development of high-performance platinum (Pt)-based electrocatalysts for the hydrogen oxidation reaction (HOR) is highly desirable for hydrogen fuel cells, but it is limited by the sluggish kinetics and severe carbon monoxide (CO) poisoning in alkaline medium. Herein, we explore a class of facet-selected Pt−nickel−indium fishbone-like nanowires (PtNiIn FNWs) featuring high-index facets (HIFs) of Pt 3 In skin as efficient alkaline HOR catalysts. Impressively, the optimized Pt 66 Ni 6 In 28 FNWs show the highest mass and specific activities of 4.02 A mg Pt −1 and 6.56 mA cm −2 , 2.0/2.1 and 13.9/15.6 times larger than those of commercial PtRu/C and commercial Pt/C, respectively, along with a competitive CO-tolerance ability. Specifically, they exhibit only 6.0% current density decay after 10000 s of operation and 25.7% activity loss after 2000 s in the presence of 1000 ppm of CO. Moreover, an isotope experiment and density functional theory (DFT) calculations further prove that the unique structure and synergy among Pt, Ni, and In endow these Pt 66 Ni 6 In 28 FNWs with an optimized hydrogen binding energy (HBE) and an advantageous hydroxide binding energy (OHBE), giving them excellent alkaline HOR properties. The combined construction of surface-skin and HIFs in PtNiIn FNWs will offer an available method to realize the potential applications of advanced non-PtRu-based catalysts in fuel cells and beyond.