In this study, an ultrasound-assisted extraction (UAE) of ellagic acid (EA) from pomegranate husk was studied according to a central composite design (CCD) matrix and analyzed under response surface methodology (RSM). Effect of several factors such as temperature (26–93 °C), sonication time (4–55 min), concentration of solvent (aqueous ethanol, 24%–75%), and solid–liquid ratio (3–16 g/mL) were evaluated. EA yield was determined by high performance liquid chromatography (HPLC) analysis and then CCD model was validated. The best extraction conditions were at 93.60 °C of extraction temperature for 55.23 min using 75.23 % of aqueous ethanol and liquid/solid ratio of 3.27 mL/g of vegetal material obtaining a recovery of EA of 19.47 mg/g. In addition, four experiments were conducted to evaluate the extent to which the individual impact of sonication and temperature on EA extraction from pomegranate husk. A positive effect combined both factors was observed. On the other hand, the results could suggest that UAE has no effect on purified ellagitannins hydrolysis under conditions used in this study, indicating that increase in the EA yield is attributed only to the cell rupture. The optimal conditions of EA extraction from pomegranate husk established in this research could be applicable in the food and pharmaceutical industry due to the UAE method presents many advantages in comparison with conventional technologies.