The efficient hydrophobization mechanism of a hydrophilic cellulose film surface with alkylketene dimer (AKD) was studied in terms of formation of beta-ketoester bonds at AKD/cellulose interfaces and their nanosized distribution analysis. AKD-treated cellulose and nanocellulose films were sequentially extracted with chloroform, hot water, and dioxane/water. Atomic force microscopy and high-resolution secondary-ion mass spectrometry were used to analyze the surface structures of the AKD-treated cellulose films and those after the sequential extraction. The results showed that the AICD molecules had melted and transformed into spherical nanoparticles, similar to 37 nm in diameter, on the film surface during heat treatment, forming "sea/island"-like structures; the film surface projection area comprised 99% hydrophilic cellulose and 1% hydrophobic AKD nanoparticles. Determination of the AKD contents in the films revealed that an extremely small amount of AKD/cellulose beta-ketoester bonds were likely to form at the AKD/cellulose interfaces during heating, clearly contributing to the hydrophobic nature of the sequentially extracted cellulose films.