The developed and confirmed RP-HPLC method is specific, precise, accurate, and reliable for the measurement of teriflunomide in tablet dosage form. An analytical quality by design approach was employed for the optimization of the RP-HPLC method by means of design of experiments and response surface methodology like Box Behnken Design (BBD) in order to achieve a good resolution. Chromatographic separation was acquired with C18 column Phenomenex C18 (250 × 4.6 mm, 5 µm), at flow rate 0.8 mL/min with the mobile phase consists of acetonitrile and water (80:20% v/v). The detection of Teriflunomide was carried out at 280 nm. The method was linear in range of 5-25 µg/mL and recovery was in range of 99.61% to 101.45%. Forced degradation study of teriflunomide was performed by RP-HPLC method which includes Acid, Base, Oxidative, Photo and Thermal degradation. Result of degradation were found within the limit.