The statistical design of the experiments combined with techniques of regression was applied in optimizing the conditions of maximum adsorption of the dye onto sepiolite. The initial pH of the dispersion exerted the greatest influence on the amounts of dye adsorbed Qe. The factorial experiments demonstrated significant antagonistic interaction between pH and ionic strength. This interaction had more influence on Qe than did the other interactions (temperature–pH, temperature–ionic strength). Ionic strength, temperature, and pH had a negative influence on Qe, is the validity of this study was limited to temperatures between 25 and 55 °C, pH between 2 and 9, and ionic strength of up to 0.1 M NaCl.