In order to solve the serious leaching problem of supported heteropoly acid catalysts in polar reaction media, 12-molybdophosphoric acid encapsulated in the supercage of Cs+-exchanged Y zeolite was prepared by the "ship in the bottle" synthesis. The influence of ion-exchange conditions and the synthesis parameters on the encapsulation of PMo12 were investigated. The obtained solid sample was characterized by X-ray diffraction (XRD), P-31 magic angle spin nuclear magnetic resonance (MAS NMR) and Fourier Transform Infrared Spectroscopy (FT-IR), and its catalytic activity in the esterification of acetic acid and n-butanol was tested. The ion-exchange time, concentration of aqueous Cs+ solution, pH value, and amount of Mo added in the synthesis mixture were revealed to influence the encapsulation very remarkably. Under the optimal conditions, 12-molybdophosphoric acid could be successfully encapsulated in the supercage of CsY zeolite, and the samples showed considerable catalytic activity and excellent reusability in the esterification reaction.