We demonstrate the design strategy of free-standing Au nanocatalysts by correlating their physicochemical characteristics with photocatalytic performance. By tailoring the particle size and surface characteristics, we found that small Au nanocatalysts called Au nanoclusters with discrete energy levels are more effective than large metallic Au nanoparticles, while the microenvironments (e.g., charge status and hydrophilicity/hydrophobicity) around the surface of Au-nanoclusters are crucial in determining the performance. With the optimized Au nanocatalyst, under visible light, decarboxylative radical addition reactions for C-C bond formation (i.e., Giese reaction) were first achieved with high yields and further utilized for the preparation of one of the bioactive γ-aminobutyric acid derivatives, pregabalin (Lyrica®), demonstrating its potential in pharmaceutical applications.