Uplift of the Tibetan Plateau since the Late Miocene has greatly affected the nature of sediments deposited in the Qaidam Basin. However, due to the scarcity of continuously dated sediment records, we know little about how minerals responded to this uplift. In order to understand this response, we here present results from the high-resolution mineral profile from a borehole (7.3–1.6 Ma) in the Basin, which shows systematic oscillations of various evaporite and clay minerals that can be linked to the variation of regional climate and tectonic history. In particular, x-ray diffraction (XRD) analyses show that carbonate minerals consist mainly of calcite and aragonite, with minor ankerite and dolomite. Evaporates consist of gypsum, celesite and halite. Clay minerals are principally Fe-Mg illite, mixed layers of illite/smectite and chlorite, with minor kaolinite and smectite. Following implications can be drawn from the oscillations of these minerals phases: (a) the paleolake was brackish with high salinity after 7.3 Ma, while an abrupt change in the chemical composition of paleolake water (e.g. Mg/Ca ratio, SO4 2− concentration, salinity) occurred at 3.3 Ma; (b) the three changes at ~6.0 Ma, 4.5–4.1 Ma and 3.3 Ma were in response to rapid erosions/uplift of the basin; (c) pore water or fluid was Fe/Mg-rich in 7.3–6.0 Ma, Mg-rich in 6.0–4.5 Ma, and K-rich in 4.1–1.6 Ma; and (d) evaporation rates were high, but weaker than today’s.