Hemoglobin (Hb)-capped gold nanoclusters (Hb/AuNCs) are synthesized, characterized and introduced as durable and high-performance ethanol oxidation electrocatalysts with superior mass and specific activities. The experimental results and computational analysis suggest that the key reasons for the excellent catalytic activity of Hb/AuNCs are: (i) Fe atoms in the heme group of Hb acting as oxophilic metal active centers, via metal–metal bond formation with the AuNCs and (ii) the presence of a protein shell effectively hindering the Ostwald ripening and aggregation of AuNCs.