Groundwater is an important drinking water source in the Lhasa River Basin, and human activities and global changes have a certain impact on groundwater in the region. To study the groundwater quality status in the Lhasa River Basin, 65 sets of groundwater samples were collected in the study area, and 31 indicators were analyzed and tested. The hydro-chemical characteristics and controlling factors of groundwater in the study area were analyzed by using methods such as mathematical statistics, correlation analysis, hydrogeochemical diagram. A comprehensive evaluation of water quality in the study area was conducted using four methods: single index highest category method, Nemerow index, fuzzy mathematics method, and entropy weight water quality index(EWQI). The results show that the overall water quality in the study area is weakly alkaline freshwater as a whole. Ca²⁺, Mg²⁺, , are the dominant ions, and the hydrochemical types are mainly HCO₃-Ca and HCO₃·SO₄ -Ca. Rock weathering, particularly the dissolution of silicate and carbonate minerals, serves as the dominant mechanism controlling hydrochemical composition. The water quality evaluation results indicate an overall preference for groundwater in the area. EWQI and fuzzy mathematics methods have evaluated that the groundwater quality in the area is mainly Class Ⅰ. The single index highest category method identifies that the main components of groundwater exceeding the standard include nitrate, ammonia nitrogen, iron manganese, and arsenic. Nitrate and ammonia nitrogen pollution likely originates from agricultural non-point sources, whereas localized Fe, Mn, and As anomalies are attributed to natural geogenic processes. Methodological comparisons demonstrate that single-factor assessment prioritizes safety thresholds, whereas EWQI and fuzzy mathematics methods better accommodate multi-indicator evaluations. Method selection should align with specific water quality parameters and functional requirements. The research results provide critical insights for groundwater pollution control and drinking water safety management in typical Tibetan Plateau watersheds.