It is of great importance to propose effective methods to quantify interfacial interaction since it directly determines foulant adhesion and membrane fouling process in membrane bioreactors (MBRs). This study developed a radial basis function (RBF) artificial neural network (ANN) to predict the interfacial interactions with randomly rough membrane surface. The interaction data quantified by the advanced extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) approach were used as the training samples for the RBF networks. It was found that, the computing time consumption for the RBF network prediction was only about 1/50 of that for the advanced XDLVO approach under same conditions, indicating the high efficiency of the RBF ANN method. Meanwhile, the calculation accuracy of the method was acceptable to get reliable results. This study demonstrated the breakthrough of the fundamental methodology related with membrane fouling. The proposed RBF ANN method has broad application prospects in membrane fouling and interface behavior research.