This study aimed to assess the prediction efficiencies of response surface methodology (RSM) and artificial neural network (ANN)-based models in terms of benzene, toluene, ethylbenzene, and xylenes (BTEX) removal from a polluted airstream using non-thermal plasma (NTP). The effect that key elements of the NTP process, including temperature, BTEX concentration, voltage and flow rate, had on the BTEX elimination efficiency was investigated using a central composite RSM design along with three ANN models including Feed-Forward Back Propagation Neural Network (FFBPNN), Cascade-Forward Back Propagation Neural Network (CFBPNN) and Elman-Forward Back Propagation Neural Network (EFBPNN) with the topology of 4-h-1. The RSM and ANN models were statistically compared using some indicators including Sum of Squared Errors (SSE), adjusted R-2, determination coefficient (R-2), Root Mean Squared Error (RMSE), Absolute Average Deviation (AAD). According to the RSM output, voltage was the most efficient variable with a coefficient proportion of 8.28. Besides, FFBPNN was the best model among the considered ANN models. Also, the R-2 achieved for ANN (FFBPNN) and RSM models were 0.9736 and 0.9656 correspondingly. Therefore, it was concluded that the ANN (FFBPNN) represents a powerful tool for modeling the BTEX removal. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.