Objective: Selective serotonin reuptake inhibitor (SSRIs) compounds are the most used compounds in the treatment of depression. The determination of chromatographic separation and quantitative determination of these compounds is very important in the clinical use of these compounds and the success of biopharmaceutical studies. For this reason, this study, it was aimed to optimize the chromatographic conditions for the quantitative determination of SSRIs in tablet formulation by Reversed phase liquid chromatography method. Material and Method: The optimum separation condition for the studied compounds was determined based on the relationship between the retention values of the compounds and the pH and the content of the mobile phase. Chromatographic determination was made on the X Terra C18 column (250 x 4.6 mm I.D., 5 μm), which is widely used for the determination of hybrid-based and basic compounds. The validation of the developed method was carried out based on the parameters of linearity, precision, and accuracy. Result and Discussion: The developed and validated method was successfully applied for the determination of active ingredients in the tablet dosage form. The experimental results of the amount of studied SSRIs in selected commercial tablets are in good agreement with the label claims. The calculated percent recoveries show that the sample preparation techniques developed for the quantification of the compounds studied are not affected by interferences. The evaluation of the obtained results showed that the developed method is suitable for the routine use of studied compounds.