Optimal operation of small hydropower stations in large-scale irrigation region is of great significance to promote the use of clean energy, reduce regional carbon emission, and protect local environments. This paper presents a study to simulate the performance of water resources system and to optimize the operation plan of a small hydropower station group in climate change scenarios, via a case study of a large-scale irrigation region, the Pihe irrigation district in Anhui, China. Results show that with a slight increase in rainfall and a slight temperature rise in the future, the current system operation plan will not be able to meet the requirement of assurance rate for urban water supply and the increase in the total power generation will be negligible. Through optimization, however, the annual average power generation will increase by 115*10~4kW·h if all the following conditions are satisfied: the flood control capacity of the Foziling reservoir increases by 6.2%, the flow plan of water supply line changes to 25.7m~3/s, and the upper limits of recharging capacity of the urban reservoir in non-irrigation and irrigation periods are altered to 0.98*10~8 m~3 and 0.59*10~8 m~3 respectively. These results indicate considerable social and economic benefits of the irrigation system.