To investigate the efficiency of a Co-Mo catalyst in HDS process, a set of experiments were designed and carried out based on central composite design (CCD) methodology in an HDS pilot plant. The designed variables included temperature, LHSV and pressure. However, the hydrogen over fresh feed ratio remained constant. The ranges of these variables were, respectively, equal to 335-361 ℃, 1.06-1.8 1/hr and 46.8-53.2 bar. The outcomes of experiments were employed to determine the coefficients of statistical models. For the clarification of the accuracy of the model, several statistical tests like ANOVA (Analysis of Variance), Lack-of-Fit test and residual squares were carried out. To optimize the operating conditions to achieve maximum sulfur removal, an optimization algorithm was employed. The outcomes revealed that the minimum sulfur content, which is 23.65 ppm in the final product, is attained at 355 ℃, 1.2 1/hr and 49.2 bar.