Predicting the hydraulic behavior of the river and flood zone determination to reduce probable damages, are among measures which in recent years has been the attention of many researchers. Mazandaran province, especially the city of Neka, each year is affected by the floods with different return periods; therefore, land use changes and the role of these changes were evaluated in flood zones. In this study, with integration of river system analysis, GIS and Remote Sensing, images of the years 2000 and 2011 were processed and Neka river hydrological response was determined in specified return periods. The results showed Pearson type 3 distribution, roughness coefficient determined by Cowan’s method and IRS image in comparison with ETM+ image, have good accuracy. With determining land use changes in the years 2000 and 2011, the area of each land use class was specified in GIS, and then attached to the HEC-GeoRAS. By determining two flood maps with return periods of 2 to 200 years, the difference of each layer was determined. Many studies determined land use only; but according to the results of this study and impact of the 14.60-percent increase in flood area, the role of changes is noticeable. This study suggests that in the flood zone determination, addition to land use designation, we should pay special attention to its changes and hydrological response of the total area to these changes, and its role in the flood zones. The simulation of river bed and flood zone in forest areas depends on land use, and deforestation in this river is one of the most important factors.