In this study, cetyl trimethylammonium bromide (CTAB) (cationic) and sodium dodecyl benzene sulfonate (SDBS) (anionic) were used to modify natural sepiolite (SEP) to obtain a type of organic sepiolite (C-S-SEP). It was further applied for adsorption of oxytetracycline (OTC), a common antibiotic in water. The changes of SEP crystal structure and physicochemical properties before and after modification were analyzed by the means of XRD, FTIR, TG, SEM/EDS, BET, XPS and zeta potential. The adsorption performance and mechanism of OTC on C-S-SEP were studied by static adsorption method. The results showed that the adsorption capacity of C-S-SEP increased significantly, and the removal rate of OTC increased from 50.26% to 99.42%. The partition coefficient of SEP and C-S-SEP was 0.356 and 2.172 mg g 1 lM 1,respectively. CTAB and SDBS were successfully loaded onto the surface of SEP without entering its interlaminar domain, and the original crystal structure of SEP was well maintained. In the range of the studied ratio, anionic and cationic surfactants had the synergistic solubilization effect. The adsorption process conformed to the pseudo-second-order kinetic model and Langmuir isothermal adsorption model. The adsorption reaction was exothermic and a process of entropy reduction. The increase of temperature was not conducive to adsorption, and the adsorption reaction was basically unaffected by the pH value.The adsorption of C-S-SEP on OTC was the result of the combination of distribution and surface adsorption. The organic modified SEP was expected to become a low-cost environmentally friendly adsorption material that can effectively remove OTC from water.