In this study the performance of ANN with feed-forward neural network (FFNN) algorithm evaluated rainfall-runoff modeling in five gauging stations in Florida State. In addition, for investigating the performance of ANN in multi-station discharge prediction, self-organizing map (SOM) clustering tool employed in order to cluster the input data with similar patterns, due to the large amount of records in multiple stations. The main aim of study is to investigate capability and accuracy of ANN based methods in multi-station discharge prediction. In order to consider multiple stations effect on watershed outlet discharge, different combinations for precipitation and discharge data of all stations with antecedent values over the watershed have been taken into account. In this way, application of the representatives from each cluster led to significantly reduction in the numbers of the input variables so that the optimal ANN structure could be proposed. Therefore, ANN as a data-driven model was trained to predict daily runoff for the Peace River basin via recorded values from July 1995 to July 2011. Three scenarios conducted the aim of research; first scenario was an integrated ANN model trained by the data of rainfall and runoff at multiple stations. The second scenario was a sequential ANN model processed with upstream discharge records in addition to rainfall data as inputs and downstream discharge values as target. Finally, third scenario was a SOM-ANN model, in which rainfall and runoff data were clustered according the homogeneity of data via (SOM). The center of each cluster as the dominant component of each cluster was imposed to ANN in order to present an optimal rainfall-runoff model over the watershed. In all scenarios, different data sets at various time lags in both rainfall and stream flow data were applied as inputs in ANN- based model to predict stream flow. Results show that ANN model coupled with SOM is useful tools for forecasting multi-station discharge and precipitation event response in the watershed. Furthermore, the comparison of scenarios lead s to select the most efficient and optimal inputs to ANN which subsequently, presents the optimal multi- station rainfall-runoff model over the watershed.