In this research, chitosan nanoparticles as an efficient and reusable adsorbent with adsorption capacity of 5.79 mg/g, surface area of 62 m2/g and pHpzc of 8.07 were applied to remove the ethinylestradiol (as a sample of estrogen) from an aqueous wastewater. The chitosan nanoparticles were characterized by SEM, XRD and FT-IR analyses. Four independent variables involving contact time, adsorbent dosage, pH, and initial concentration of estrogen were applied to design the experiments by Design Expert software (CCD under RSM). In fact, number of experiments was minimized and the operating conditions were optimized for the maximum estrogen removal. The results indicated that three independent variables (contact time, adsorbent dosage, and pH) increment increased the estrogen removal while the estrogen initial concentration enhancement decreased the removal due to the concentration polarization phenomenon. The optimum conditions for the estrogen removal (92.50%) on the chitosan nanoparticles were found at contact time of 220 min, adsorbent dosage of 1.45 g/l, pH of 7.3 and estrogen initial concentration of 5.7 mg/l. Moreover, the Langmuir isotherm and pseudo-second order models could properly legitimize estrogen adsorption process on the chitosan nanoparticles.