Bisphenol A (BPA), an endocrine disrupting compound, is of concern because of its wide presence throughout the environment and its harmful effects. The present study aimed to prepare an eco-friendly, low-cost, and efficient adsorbent for removal of BPA from wastewater. A natural Tunisian clay was used as a raw material. First, the clay was purified and then modified with hexadecyltrimethylammonium bromide (HDTMA) using microwave heating. The optimal conditions for clay modification were as follows: activation ratio = 0.3:(g/g), solid/liquid ratio = 5%, and microwave heating condition (2:min, 100:W). The purified and modified clays, abbreviated as HP and HMH, respectively, were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and nitrogen adsorption/desorption analysis (BET). Adsorption tests were conducted in a batch reactor process under various conditions. The tests showed that the BET specific surface area of HMH is considerably smaller than that of HP, whereas the basal spacing increased from 14.99 to 22.07 Å after modification, indicating the success of HP organophilization. The adsorption of BPA onto HMH was not affected by the pH of solution between 2 and 10 and only slightly by temperature variation from 23 to 50°C, but was affected significantly by the initial concentration of BPA, contact time, and organo-clay dose. At equilibrium, the data obtained were fitted to Langmuir and Freundlich models. The best fit was obtained by the Langmuir model with a maximum monolayer adsorption capacity of 217.39 mg/g at 23°C. The thermodynamic study suggested that the removal of BPA by HMH was spontaneous (ΔG < 0), exothermic (ΔH < 0), and favorable. The present study demonstrated that HMH synthesized from an abundant and cheap natural clay could be used successfully as a low-cost adsorbent for the removal of BPA from wastewater.