A new nano system based on drug/clay minerals is sought as an alternative to the current options due to the limitations of the conventional treatment. In this study, experimental conditions, such as pH, reaction duration and initial drug concentration, were evaluated to obtain systems based on the anticancer drug tamoxifen (TMX) and montmorillonite. Equilibrium and kinetic studies were developed for montmorillonite (VHS)/TMX at pH values in the range of 1.5 to 7.0 for reaction times of 1 to 720 min and drug concentrations of 533 to 2300 mg·L⁻¹. The solids were characterized by using X-ray diffraction and middle infrared spectroscopy (MID). The interaction of TMX with montmorillonite was pH-dependent with a higher adsorption at pH 5.5 (402.63 mg·g⁻¹). For all pH values, intercalation of the drug was the preponderant mechanism of interaction. The system was described by a pseudo-second-order model. In the equilibrium study, the data adsorption was fitted to Langmuir model. Therefore, the reaction between TMX and montmorillonite was effective, and the best experimental conditions to obtain the studied hybrids were at pH 5.5 for 720 min and 2300 mg·L⁻¹ drug concentration.