Few proxies can provide quantitative reconstructions of past continental climatic and hydrological changes. Here, we report the first alkenone-based reconstruction of late Holocene temperature and salinity changes in Lake Qinghai, China. The alkenone-temperature proxy (U^k′ ₃₇) indicates up to a 1°C change in mean annual air temperature or a 2°C change in summer lake water temperature during the late Holocene. Oscillating warm and cold periods could be related to the 20th century warm period, the Little Ice Age, the Medieval Warm Period, the Dark Ages Cold Period, and the Roman Warm Period. The relative importance of C_37:4 alkenone to total C₃₇ alkenone production (%C_37:4) fluctuated between 15–45%, with higher values during warm periods, suggesting that lake water was also fresher during these periods. The coupled late Holocene surface temperature and salinity changes suggest that Asian monsoons strongly influenced the climate of the Lake Qinghai region.