Thin-film nanocomposite (TFN) membranes based on nanomaterial-embedded ultrathin polyamide layers have been extensively studied as an energy-efficient material for reverse osmosis (RO) desalination. Although several studies have reported that TFN membranes with zeolitic imidazole frameworks (e.g., ZIF-8) showed improved RO performances, attributed to its intrinsic microporosity and high specific surface area, an in-depth study on the role of ZIF-8 nanoparticles in selective polyamide layers has not yet been published. Here we synthesized ZIF-8 nanoparticles with different average sizes (60, 150, and 250 nm) and investigated the effects of particle size on the separation performance of TFN membranes. Interestingly, it was found that the deposition of ZIF-8 nanoparticles on the microporous polysulfone (PSf) support prior to interfacial polymerization of the polyamide layer was influenced by ZIF-8 particle size. Small-sized ZIF-8 nanoparticles showed the highest surface coverage, which is consistent with the classical particle deposition theories. The interface area between ZIF-8 nanoparticles and polyamide matrix varied with particle size, ultimately affecting the RO performance of TFN membranes. Our results firstly reveal that the amount of particle deposition prior to interfacial polymerization could be strongly influenced by particle size, emphasizing the importance of particle deposition for the further studies on nanoparticle-embedded TFN membranes.