Abstract The ppt to ppb sulfamethoxazole (SMX) entering natural water bodies and possibly present in drinking water is not significantly removed and remain persistent and toxic by conventional adsorbents. Aminated chitosan/cellulose nanocomposite microspheres (ACNM) were prepared by in-situ solid phase grafting methods for low concentration of SMX removal. The physical and chemical properties of ACNM were characterized by SEM, FTIR and XRD etc. 10 mg L−1 SMX was used to simulate the low concentration of SMX in the aqueous phase, SMX adsorption on ACNM could reached the equilibrium within 30 min. The adsorption process was better kinetically fitted with the pseudo-second-order kinetic model and Langmuir isothermal model, suggesting that monolayer chemical adsorption was the dominant adsorption process. The removal efficiency of SMX reached 99.18%, and the adsorption capacity was 13.59 mg g−1. The adsorption mechanism was also studied. ACNM retained 96.8% of the initial adsorption capacity after 3 cycles. Column adsorption experiments were studied to determine the best adsorption conditions.