<p>Membrane-less organelles (MLOs), formed by liquid-liquid phase separation (LLPS) of biomolecules in cells, play crucial roles in cellular function such as gene expression, epigenetics, cellular metabolism, and so on. Moreover, the function of MLOs is closely related to the size of their droplets. Synthetic coacervates, which mimic MLOs, show great potential in cell biomimicry, drug delivery, and functioning as nanoreactors. However, the droplet size regulation of coacervates excluding concentration is challenging. In this work, synthetic coacervates are formed by poly(hydroxypropyl acrylate) (PHPA), which undergoes lower critical solution temperature (LCST)-type coacervation driven by hydrophobic interactions under physiological conditions. The size of the coacervate droplets is regulated by incorporating a more hydrophobic block, poly(di(ethylene glycol) ethyl ether acrylate) (PDEGA); the droplet size decreases from 5 µm to 234 nm as the PDEGA block length increases. Additionally, liquid-to-solid phase transition (LSPT) is observed with further increase in the PDEGA block. Thus, both droplet size and LSPT are controlled by the hydrophobicity of the block copolymers. The LCST-type coacervate shows thermal protection of enzymes such as glucose oxidase, which decreases as the size of coacervate droplets decreases, while the precipitates offer no protection activity. Furthermore, glucose oxidase (GOx) retains over 85% of its activity after 3 h of treatment at 60 °C with PHPA₄₄ coacervate. The hydrophobicity-tuned size control of coacervate droplets and LSPT bring insight into the molecular mechanism of coacervate phase change and facilitates the design of coacervate for biomimicking applications.</p>