To reflect comprehensively the health statement of the Lhasa River main stream, a river health evaluation index system including 14 indexes involving hydrological water resources, water quality, biology, habitat, and service functions was constructed based on the characteristics of the Lhasa River and domestic and foreign research. The health evaluation index system was applied to the Lhasa River. The data used in the evaluation came from data collection, literature research, and field monitoring and investigation. The evaluation results showed that the Lhasa River is generally in a relatively healthy state, and the health statement of the upper reaches was better than the middle and lower reaches. The water quality of the upper reaches fulfilled the requirement of a Class I water function area during the dry season; however, in the wet season, ammonia nitrogen content exceeded the concentration limit prescribed for a Class I water function area. The total water qualification rate was 50% and scored 50. The remaining indexes of the upper reaches scored more than 75. Affected by hydropower stations and irrigation projects, the degree of variation in the flow process, river connectivity barrier, and family biotic index scored 0, 25, and 45 respectively in the middle reaches; ecological base flow security degree, invasive percentage of exotic fish, and river stability scored between 50 and 75; the other indexes of midstream scored over 75. Degree of variation in the flow process and invasive percentage of exotic fish scored 0 for downstream; river connectivity barrier scored 25; family biotic index scored 45; river stability scored 68; the other indexes of the lower reaches scored more than 75. From a river health perspective, the future management of the Lhasa River basin should focus on non-point source pollution from wet land, the comprehensive effect of hydropower station and irrigation projects, and the invasion of the river by exotic fish.