Glacial and permafrost hydrogeology is a cutting edge topic in the past decades. As the third pole of the world, Qinghai-Tibetan Plateau (QTP) is featured by its mountainous glaciers and widely distributed permafrost, therefore, can be regarded as an ideal natural laboratory to investigate how the groundwater/surface interaction and the associated biogeochemical cycling are regulated by glaciers and permafrost. From 2015-2018, comprehensive field campaigns have been made to investigate the hydro-geochemical parameters from different water endmembers (groundwater, porewater from hyporheic zone (HZ), lake water, stream water and precipitation) in in three representative headwater water catchments of QTP: Nyang headwater catchment (glacier and permafrost influenced); Parlung Zangbo headwater catchments (glacier dominated); and Yellow River headwater catchment (permafrost dominated). We investigated the multiple isotopes such as stable isotopes, radon-222, and radium isotopes, together with other geochemical parameters, such as nutrients, carbon system constituents, and major irons. The transient storage reactive transport model of 222Rn and radium isotopes are deployed to quantify the groundwater inflow rates, hyporheic exchange rates, hyporheic depths, and water residence time of HZ. Based on the depictions of groundwater surface interactions, the nutrient and dissolved inorganic carbon reactive transport model under transient storages are constructed to quantify the carbon-nitrogen cycling for the headwater catchments in QTP. The spatial distributions of groundwater inflow and hyporheic exchange rates are discussed with the geomorphological metrics of slopes, channel depths, width, sinuosity, upland contribution areas, HZ depths, and HZ residence time. The scaling results of HZ exchange rates and geomorphological parameters are further compared with the HZ exchange regression models derived from numerical modeling. Moreover, the roles of the permafrost and glacier coverage of the upland contribution areas on the the groundwater inflow rate distributions are systematically examined. The influences of groundwater, hyporheric exchange rates, glacier/permafrost coverages, geomorphological settings on the nutrient and carbon export and cycling are fully explored and conceptualized. The study makes the first attempt to quantify the groundwater/interaction and the mediated biogeochemical cycling based on multiple isotopes in the QTP and will shed new lights how the glacier and permafrost influences the groundwater surface interaction in the headwaters in QTP and other areas with similar settings.