The complexity of reactions and kinetic is the current problem of photodegradation processes. Recently, artificial neural networks have been widely used to solve the problems because of their reliable, robust, and salient characteristics in capturing the non-linear relationships between variables in complex systems. In this study, an artificial neural network was applied for modeling p-cresol photodegradation. To optimize the network, the independent variables including irradiation time, pH, photocatalyst amount and concentration of p-cresol were used as the input parameters, while the photodegradation% was selected as output. The photodegradation% was obtained from the performance of the experimental design of the variables under UV irradiation. The network was trained by Quick propagation (QP) and the other three algorithms as a model. To determine the number of hidden layer nodes in the model, the root mean squared error of testing set was minimized. After minimizing the error, the topologies of the algorithms were compared by coefficient of determination and absolute average deviation.