Nanoparticle assemblies (NPAs) have attracted tremendous interests of various research communities. The particle-size-effect on mechanical properties of NPAs is first ever systematically studied. With decreasing the particle size d from 300nm to 10nm, the SiO2 NPAs become drastically harder (~39x), stiffer (~15x), and tougher (~12x). The results are consistent with the data scattered in the literature for various nanoparticle (NP) systems, indicating a fundamentally universal d-effect for all NPAs. A model is developed to correlate the hardness and the NP junction (NPJ) strength f. Here, f is mainly due to van Der Waals interaction, roughly a constant (140nN) for d =100~300nm, and then f decreases with decreasing d from ~100nm. The deformation mechanism of NPAs is shear plasticity involving shear breaking of NPJs. The fundamental mechanism for the d -effect is that, with decreasing d, the NPJ's planar density largely increases while f has little change. Moreover, three deformation mechanisms of NPAs: (1) nanoparticle dislodging, (2) shear-band formation, and (3) delamination/cracking, are naturally d-dependent. These new findings can provide important insights into the fundamental understanding of the inter-NP interaction, the mechanical behavior of the NPAs, and the design of robust NP-based devices.