Bimetallic Ni_xCu_(10−x)/γ-Al₂O₃ catalysts (where x is the mass fraction of Ni) with different Ni/Cu mass ratios were prepared. The catalysts were characterized by X-ray diffractometry, N₂ adsorption–desorption, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, H₂-temperature programmed reduction, and transmission electron microscopy. The effect of Ni/Cu mass ratio on benzofuran hydrodeoxygenation was investigated in a fixed-flow reactor. Cu addition improved the NiO reducibility. The strong interaction of Ni and Cu led to the formation of smaller and highly dispersed CuO and NiO species over γ-Al₂O₃, which favors an improvement in catalytic activity. Among the as-prepared catalysts, the Ni₅Cu₅/γ-Al₂O₃ showed the highest deoxygenated product yield (79.9%) with an acceptable benzofuran conversion of 95.2%, which increased by 18.3% and 16.9% compared with that of the monometallic Ni/γ-Al₂O₃ catalyst. A possible reaction network was proposed, which would provide insight into benzofuran hydrodeoxygenation over the Ni₅Cu₅/γ-Al₂O₃ catalyst.