Calcite depression is the most effective physicochemical process to valorize fluorine mineral. This process is achieved by adsorption of tannic acid, as the commonly used reagent, onto calcite. Adsorption investigation is very important in mineral processing. The present work focuses on optimization of physicochemical parameters of tannic acid adsorption onto calcite. Experimental study is carried out by a response surface methodology based on Box-Behnken design. Obtained results are exploited to develop a statistical model. Analysis of variance and residuals are performed to check the significance of tested models. Among these models, Cox-Box model predicts very well the obtained experimental data. This model shows that initial tannic acid concentration and solution pH as well as their interactions are the most significant parameters. Optimal conditions are achieved using the obtained statistical model. The present investigation is an important preliminary step to better understand calcite flotation behavior using tannic acid as a depressant.