Phenolic compounds were extracted from pistachio hull using microwave-assisted solvent extraction (MASE). The effects of four parameters, microwave power, extraction time, solvent to sample ratio, and ethanol concentration were evaluated. The extraction conditions were optimized by response surface methodology to enhance the total phenolic content (TPC). Optimal conditions were found as 140 W microwave power, 4.5 min extraction time, 19:1 (v/w) solvent to sample ratio, and 56% ethanol concentration to get maximum TPC (62.24 mg GAE/g dry hull). Also, MASE was compared with conventional solvent extraction (CSE) and MASE gave higher TPC, yield, and antioxidant activity.