Novel heteropolyanion-based ionic liquids (HPA-ILs) were obtained by combining Keggin heteropolyanions and organic cations and used as catalysts for an esterification reaction. The kinetic behaviors in the esterification of diethylene glycol monobutyl ether (DGBE) with acetic acid in the presence of HPA-ILs as catalysts were investigated systemically. Different types of HPA-ILs were used for the esterification of DGBE. Compared with H2SO4, H3PW12O40, and Amberlyst-15 resins, [BSEt3N](3)PW12O40 and [BSmim](3)PW12O40 exhibited excellent catalytic activities. The influences of reaction temperature, catalyst dosage, and reactant molar ratio on the conversion of DGBE were studied in detail. The kinetic data were successfully correlated by a pseudohomogeneous (PH) model in the temperature range of 343.15-363.15 K. The simulation values obtained by the kinetic model were in good agreement with the experimental data. Moreover, [BSEt3N](3)PW12O40 and [BSmim](3)PW12O40 could be easily recovered and reused six times without any obvious decrease in catalytic activity.