The response surface methodology in combination with a Box–Behnken experimental design was performed to optimize the extraction conditions, resulting in a maximum yield of the total phenolic content (TPC) from the leaves of Pistacia atlantica. The ranges of the examined independent variables (factors), i.e. extraction time (24–72 hours), liquid-to-solid ratio (30 : 1–50 : 1 ml solvent per g dry leaf) and extraction temperature (35–55 C), were identified by preliminary experiments. Quadratic polynomial regression models were fitted through the experimental results. They showed acceptable coefficients of multiple determinations. From the models, the liquid-to-solid ratio was found to have the most influence on the extraction of TPC. The optimum extraction conditions were found to be 72 h extraction time and 50 : 1 ml g1 liquid-to-solid ratio. For the extraction temperature, rather high values (about 50 C) were found to be the best. Using the optimized conditions, the TPC varied from 256 to 306 mg gallic acid equivalents per g dry leaf in different sample types.