An effective cocatalyst is crucial for enhancing the visible photocatalytic performance of the hydrogen generation reaction. By using density-functional theory (DFT) and frontier molecular orbital (FMO) theory calculation analysis, the hydrogen adsorption free energy (ΔG_H) of Ni–Mo alloy (458 kJ·mol^–1) is found to be lower than that of Ni itself (537 kJ·mol^–1). Inspired by these results, the novel, highly efficient cocatalyst NiMo@MIL-101 for photocatalysis of the hydrogen evolution reaction (HER) was fabricated using the double solvents method (DSM). In contrast with Ni@MIL-101 and Mo@MIL-101, NiMo@MIL-101 exhibited an excellent photocatalytic performance (740.2 μmol·h^–1 for HER), stability, and high apparent quantum efficiency (75.7%) under 520 nm illumination at pH 7. The NiMo@MIL-101 catalyst also showed a higher transient photocurrent, lower overpotential (−0.51 V), and longer fluorescence lifetime (1.57 ns). The results uncover the dependence of the photocatalytic activity of HER on the ΔG_H of Ni–Mo (MoNi₄) alloy nanoclusters, i.e., lower ΔG_H corresponding to higher HER activity for the first time. The NiMo@MIL-101 catalyst could be a promising candidate to replace precious-metal catalysts of the HER.