In order to evaluate the impact of hydropower exploitation on a river’s ecological environment, we established an evaluation index system, which includes 22 factors falling within the scopes of the water environment, ecological environment, and social environment, based on the unique geographical and climatic conditions and social and economic development in Tibet. With comprehensive consideration of various factors, we determined the standards for classification of the indices. We used the comprehensive index method to construct the evaluation model, and classified the evaluation results into five categories: insignificant influence, less insignificant influence, moderate influence, less significant influence, and significant influence. A case study at the Manla Hydropower Station showed that the exploitation of hydropower had little impact on the station, and the application results were consistent with the actual situation.