This study investigated the application of experimental design methodology to optimization of conditions of air-plasma and oxygen-plasma oxidation of N, N-Dimethyl-4-nitrosoaniline (RNO). The reactions of RNO degradation were described as a function of the parameters of voltage (X1), gas flow rate (X2) and initial RNO concentration (X3) and modeled by the use of the central composite design. In pre-test, RNO degradation of the oxygen-plasma was higher than that of the air-plasma though low voltage and gas flow rate. The application of response surface methodology (RSM) yielded the following regression equation, which is an empirical relationship between the RNO removal efficiency and test variables in a coded unit: RNO removal efficiency (%) = 86.06 + 5.00X1 + 14.19X2 - 8.08X3 + 3.63X1X2 - 7.66X2 2 (air-plasma); RNO removal efficiency (%) = 88.06 + 4.18X1 + 2.25X2 - 4.91X3 + 2.35X1X3 + 2.66X1 2 + 1.72X3 2 (oxygen-plasma). In analysis of the main effect, air flow rate and initial RNO concentration were most important factor on RNO degradation in air-plasma and oxygen-plasma, respectively. Optimized conditions under specified range were obtained for the highest desirability at voltage 152.37 V, 135.49 V voltage and 5.79 L/min, 2.82 L/min gas flow rate and 25.65 mg/L, 34.94 mg/L initial RNO concentration for air-plasma and oxygen-plasma, respectively.