Due to the effects of anthropogenic activities and natural climate change, streamflows of rivers have gradually decreased. In order to maintain reliable water supplies, reservoir operation and water resource management, accurate streamflow forecasts are very important. Based on monthly flow data from five hydrological stations in the middle and lower parts of the Hanjiang River Basin, between 1989 and 2009, we consider an efficient approach of adopting the gene expression programming model based on wavelet decomposition and de-noising (WDDGEP) to forecast river flow. Original flow time series data are initially decomposed into one sub-signal approximation and seven sub-signal details using the dmey wavelet. A wavelet threshold de-noising method is also applied in this study. Data that have been de-noised after decomposition are then adopted as inputs for WDDGEP models. Finally, the forecasted sub-signal results are summed to formulate an ensemble forecast for the original monthly flow series. A comparison of the prediction accuracy between the two models is based on three performance evaluation measures. Results show that the new WDDGEP models can effectively enhance accuracy in forecasting streamflow, and the proposed wavelet-based de-noising of the observed non-stationary time series is an effective measure to improve simulation accuracy.