Atom-precise metal nanoclusters (NCs) have garnered considerable attention due to their photoluminescence and catalytic properties arising from the quantum confinement effect and metal-ligand interaction. However, the tendency of NCs to aggregate under reaction conditions hinders their catalytic activity. Surface-protecting ligands can enhance the stability, but they often reduce surface exposure and, consequently, catalytic activity. The incorporation of surface-cleaned clusters into the pores of metal–organic framework (MOF) is highly desirable. Here, we constructed a hybrid structure in which Zr-based MOF, UiO-66-NH2, is grown directly on the surface of the [Au9(PPh3)8](NO3)3 cluster. During the nanocluster-templated growth of MOF, the triphenylphosphine ligand was removed, yielding a surface-clean gold cluster-MOF composite material. An integrated experimental-theoretical analysis revealed that the ligand-free Au clusters occupy the pores of the MOF framework. This composite exhibited an overpotential of 65 mV and demonstrated a high chronopotentiometric stability in the hydrogen evolution reaction (HER). For the horseradish peroxidase (HRP)-mimicking reaction, the Michaelis–Menten constants (Km) for H2O2 and TMB were determined to be 0.1 and 2.7 mm, respectively. Experimental and computational studies demonstrated that the MOF-induced confinement, coupled with NH2 group interactions within its pores, modulates catalyst–substrate interactions, thereby improving the catalytic performance and stability of the composite.