Salix psammophila (SP), a solid waste abundantly available, was applied as a precursor to prepare the activated carbon by chemical activation method using phosphoric acid (H3PO4). Response surface methodology based on Box-Behnken design was used to optimize the prepared conditions of activated carbon. The effects of concentration of H3PO4, activation temperature and activation time on the adsorption performance (expressed by the adsorption capacity of ciprofloxacin hydrochloride (CIP) and norfloxacin (NOR)) were investigated. The optimum conditions were obtained using H3PO4 concentration of 67.83%, activation temperature of 567.44 °C and activation time of 86.61 min. The optimum activated carbon (SPAC) was characterized with scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), Brunauer–Emmett–Teller (BET) and Fourier transform infrared spectroscopy (FTIR). The adsorption behavior of CIP and NOR on SPAC was carried out and the mechanisms for the adsorption process were proposed. The equilibrium data were fitted by the Freundlich and Langmuir isotherm models, which resulted in 251.9 mg/g and 366.9 mg/g of the maximum monolayer adsorption for CIP and NOR at 25 °C, respectively. The best fitted kinetic model was pseudo-second-order, implying that chemisorption dominated in the adsorption process. This study indicated that activated carbon based on Salix psammophila (SPAC) was an excellent adsorbent for removing fluoroquinolone antibiotics from aqueous solutions.