Clinoptilolite modified by hexadecyltrimethylammonium bromide (HDTMA-Br) was used to simultaneously remove copper and hexavalent chromium from aqueous solutions. The surface properties of HDTMA-modified natural zeolite (HMNZ) were characterized using scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), zeta potential and Fourier transform infrared spectroscopy (FTIR) techniques. SEM images showed that surfactant is adsorbed on the surface of the zeolite, which is confirmed by the FTIR result. The results from BET demonstrated a reduction in the specific surface area and pore volume due to the presence of surfactant molecules on the external surface of zeolite. The effects of important parameters on adsorption efficiency of Cu2+ and Cr (VI) were evaluated by Box-Behnken design. The Langmuir isotherm provided the best fit to the equilibrium data of Cu2+ and Cr (VI), with the maximum adsorption capacity of 0.068 and 0.0093(mmol), respectively. The film diffusion mechanism was found to control the mass transfer, and the adsorption reactions were computed as endothermic for Cu2+ ( = 17.58 kJ) and exothermic for Cr (VI) ( −26.18 kJ). The results indicated that surfactant modification changes the surface charge of zeolite from negative to positive, which makes zeolites economic adsorbents with the possibility of simultaneous removal of cations and oxyanions. The results also showed that the removal efficiency of Cr (VI) increases in the presence of copper cations due to there being more positive sites on the adsorbent surface.