Abstract: The length-scale dependence theory established by Lum, Chandler and Week provided a new insight into interpreting, studying and applying hydrophobic interaction. Hydrophobic hydration free energy decreases with the volume of solute at small length regime (< 1 nm) and increases with the surface area of solute at a larger length regime (> 1 nm). The crossover length near 1 nm indicates an entropic and enthalpic co-dominant hydration process at micro level which is distinct to the macro-level phenomenon. In this review, we showed the dependence of hydrophobic hydration free energy on temperature, pressure and additives. Especially, single-molecule force spectroscopy was introduced to provide a method to investigate hydrophobic interaction with respect to polymers. Furthermore, various applications relevant to hydrophobic interaction were represented to inspire deeper researches and explorations. Moreover, hydrophobic interaction underlying the protein folding and membrane assembly was further understood based on these promising progresses.

Key words: Hydrophobic Interaction, Length-scale Dependence, Single-Molecule Force Spectroscopy; Driving Force, Protein Folding, Membrane Assembly