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Investigation of the impact of climate change on water resources is very necessary in dry and arid regions. In the first part of this paper, the climate model Long Ashton Research Station Weather Generator (LARS-WG) was used for downscaling climate data including rainfall, solar radiation, and minimum and maximum temperatures. Two different case studies including Aji-Chay and Mahabad-Chay River basins as sub-basins of Lake Urmia in the northwest part of Iran were considered. The results indicated that the LARS-WG successfully downscaled the climatic variables. By application of different emission scenarios (i.e., A1B, A2, and B1), an increasing trend in rainfall and a decreasing trend in temperature were predicted for both the basins over future time periods. In the second part of this paper, gene expression programming (GEP) was applied for simulating runoff of the basins in the future time periods including 2020, 2055, and 2090. The input combination including rainfall, solar radiation, and minimum and maximum temperatures in current and prior time was selected as the best input combination with highest predictive power for runoff prediction. The results showed that the peak discharge will decrease by 50 and 55.9% in 2090 comparing with the baseline period for the Aji-Chay and Mahabad-Chay basins, respectively. The results indicated that the sustainable adaptation strategies are necessary for these basins for protection of water resources in future.