The river and groundwater are significant components of hydrological cycle, and the interaction between these two water resources attracted a great attention recently. Over the years, several methods have been used for the study of the water exchanges between these resources. In this research, a combined approach including hydraulic head measurements, hydrochemistry, and water balance calculations is applied to the assessment of the river–aquifer interactions. The study area is located in the north part of the Dezful–Andimeshk district in the southwest of Iran. The Dez River is the major surface water body that interacts with groundwater in this area. The Dez dam has been constructed on this river in the northern part of the study area. In this study, a series of water measurements including river water stages and discharge monitoring at Dez dam site and Dezful hydrometric station, groundwater table measurement in the piezometric network, and chemical analysis of river and groundwater were carried out for the evaluation of river–aquifer interaction. In order to monitor river and groundwater in the study area, a monitoring network including a hydrometric station (near the Dezful city), 38 piezometers, and 23 water quality monitoring wells have been established by the Khuzestan Water and Power Authority (KWPA). Data of the monitoring network were used for the evaluation of temporal variation of river and groundwater interaction in this research. The discharge measurements of the Dez dam site and Dezful hydrometric station in a 47-year period (1964–2011) shows that the water volume is decreased between these two stations. In addition, examining the time series of river stage and groundwater fluctuations in the study area shows that the groundwater table and river water stage variations have similar patterns. This similar pattern is an observant indication of groundwater and surface water interactions that is confirmed by the interpretation of groundwater potentiometric map of the study area. Following these conclusions, the hydrochemical measurements also were used for the assessment of the Dez River and groundwater connectivity. The surveys showed the similar patterns in the temporal variation trends of chemical characteristics (especially chloride ion) of the Dez River and groundwater as a base for connectivity of these resources. For better assessment of the river–aquifer interaction, 69 groundwater samples were collected from the abstraction wells in August 2012. The physicochemical analysis results show the river influences the groundwater quality. That is, the amounts of electrical conductivity (EC), temperature, and anions such as chloride, sulfate, and nitrate show a notable decrease in river-adjacent wells. Finally, for the quantifying of river–aquifer exchange rate, a simple water balance was formulated. This water budget also confirmed the Dez River role in the hydrologic balance of the study area, and according to calculation, the water infiltration from the riverbed was estimated to be more than 8 % of the aquifer recharge. This research shows the losing nature of the Dez River and its influence on the underlying groundwater quality in the study area.