The present study developed, evaluated and compared the prediction and simulating efficiency of both, the response surface methodology (RSM) and adaptive neuro-fuzzy inference system (ANFIS) approaches for oil removal using a liquid-liquid hydrocyclone (LLHC) from surfactant and polymer (SP) produced water. Six parameters were involved in the process: The surfactant concentration, polymer concentration, salinity, initial oil concentration, feed flowrate and split ratio. For RSM, D-optimal design was used, while the ANFIS model was developed in term of this process with the Gaussian membership function. All models were compared statistically based on the training and testing data set by the coefficient of determination (R2), root-mean-square error (RMSE), average absolute percentage error (AAPE), standard deviation (STD), minimum error, and maximum error. The R2 for RSM and the ANFIS model for the testing set were of 0.972 and 0.999, respectively. Both models made good predictions. Trend analysis has been done to confirm the applicability of the models. From the results, it shows that the ANFIS model was more precise compared to the RSM model, which proves that the ANFIS is a powerful tool for modelling and optimizing the efficiency of the oil removal from the LLHC in the presence of SP. © 2013 IEEE.