A study was carried out by ultraviolet-visible (UV-vis) and Fourier transform infrared (FTIR) spectroscopies to establish the efficiency of adsorption of fluoxetine hydrochloride (FLU), onto a crosslinked β-cyclodextrin-carboxymethylcellulose (β-CD-CMC) polymer. The adsorption was performed in mixtures containing aqueous FLU solution at 20 mg/L and 0.01-0.30 g of the β-CD-CMC polymer, at 25 °C, and atmospheric pressure under stirring. The results have revealed that the adsorption is a rapid process and the polymer possesses a high affinity for FLU with an adsorption capacity of 5.076 mg of FLU/g of polymer. This adsorption may involve the formation of a stable inclusion compound β-CD-CMC/FLU through the penetration of the FLU aromatic ring (A and/or B) into the β-CD cavity, and a physical adsorption with the polymer network. The inclusion compound can be stabilized by the formation of H-bonds between the -CF(3) group of FLU and the 6'-OH group of β-CD, and van der Waals interactions between the FLU aromatic ring and β-CD cavity. The data from a kinetic study have also indicated that the adsorption process was well described by the pseudo-second-order kinetic model, in which the initial adsorption rate and constant were estimated at 1.938 mg/g min and 0.075 g/mg min, respectively. Moreover, the results of adsorption equilibrium fitted the Freundlich isotherm, indicating a multilayer coverage and heterogeneous surface. Together, these results suggest that the adsorption of FLU onto the crosslinked β-CD-CMC polymer could constitute an advantageous technology for removing this commonly used antidepressant drug from wastewater due to the high adsorption capacity of the polymer and non-toxic character of β-CD to humans and environment.