17β-estradiol (E2) is a typical endocrine disrupting compounds (EDCs) commonly found in wastewater and surface water, and is considered to cause potential environmental risks. In this paper, response surface methodology (RSM) was used to explore the optimal experimental conditions of the removal of E2 from wastewater with green-synthesized iron nanoparticles (Fe NPs) to activate peroxydisulfate (PDS). The results showed that the quadratic polynomial model established by RSM was significant, while the mismatch term was not significant, and the model had good fitting performance. When the initial concentration of E2 was 3 mg·L^-1, the E2 removal rate reached 99.3% under the conditions of Fe NPs dosage of 0.09 g·L^-1, oxidant PDS concentration of 6 mmol·L^-1, pH of 3, and reaction temperature of 30 ℃. The electron paramagnetic resonance (EPR) technology and quenching experiment verified that the activation of PDS by Fe NPs mainly produced SO_4^·- and ·OH. After 4 cycles of reuse, Fe NPs still had high catalytic activity, with a degradation efficiency of 90.0% for E2, indicating that green-synthesized Fe NP is an efficient Fenton-like catalyst.