Catalytic hydrogen combustion (CHC) plays a crucial role in enhancing the safety and efficiency of fuel cells and electrolysers, thereby promoting the H2 economy. To increase the catalytic activity of supported metal particles for CHC, the active surface area can be increased through Ru fine dispersion, and intrinsic activity can be enhanced by optimising metal-support interactions (MSIs). In this study, we report the synthesis and CHC performance of highly dispersed Ru sub-nanoparticles on a gamma Al2O3 support with various Ru loadings. A clear correlation between Ru loading and CHC mass activity was identified. The highest mass activity is achieved at 1 wt% Ru, with a yield of 5.7 mmolH2 mol-1Ru s-1 at 80 degrees C. Lower Ru loadings lead to a strong MSI and subsequently to a lower Ru0/Ru-O ratio. Further, higher Ru loadings decrease metal dispersion, reducing CHC activity. Operando diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations confirmed the role of OH groups as key intermediates in the CHC mechanism over the Ru-gamma Al2O3 catalyst. Our findings highlight the impact of Ru nanoparticle size engineering on CHC mass activity and provide mechanistic insights and design principles for the development of highly active Ru catalysts, showing a way forward to achieve safer, integrated and efficient CHC utilisation.