The oxygen based membrane biofilm (O-MBfR) has been proved to be a novel technology in treating greywater (GW) and response surface methodology (RSM) was used to model the removal of chemical oxygen demand (COD) and total nitrogen (TN) with operation parameters COD/TN ratio, system pH and lumen air pressure (LAP). Results indicated that the all target single factors affect GW treatment efficiency, and the regression model with central composite design (CCD) showed good agreement with the experimental results with high R and R2 adj values (all >0.97) for all the target responses. Statistical evaluation revealed that system pH was the most significant parameter affecting COD and TN removal, followed by COD/TN ratio and LAP. The interaction between COD/TN ratio and system pH also played an important role on the GW treatment. The optimized maximum removal of COD (96.48%) and TN (133 g N/m-day) were achieved with the COD/TN ratio 17.76 g COD/g TN, system pH 7.10 and LAP 1.00 psi. Thus, RSM combined with CCD could be used for predicting the organics and nitrogen removal during GW treatment in the O-MBfR.