This is a diatom oxygen isotope record from Lake Kotokel (southern Siberia, Russia), with implications for responses of the lake system and its environment to global change over the past 46 cal. ka BP. The δ¹⁸O diatom values vary between +23.7 and +31.2‰ over the record. The results present mainly diatom assemblages of summer blooming periods, except for the time span between 36 and 32 cal. ka BP, when the isotopic signal records mainly a shift from summer to spring blooming conditions. Possible water temperature changes only partly explain the changes in the isotopic record. The observed isotopic patterns are mainly produced by isotope changes in lake water in response to variations in air temperature, hydrology, and atmospheric circulation in the region. During Marine Isotope Stage (MIS) 2 (Last Glacial maximum), high δ¹⁸O diatom resulted from rapid evaporation and low fluvial inputs. The relatively high δ¹⁸O diatom values during the first half of MIS 1 (Holocene interglacial) suggest an increased portion of summer precipitation associated with southern/southeastern moisture transport. The decrease in δ¹⁸O diatom values during the second half of MIS 1 is due to the overall hemispheric cooling and increased moisture supply to the area by the Atlantic air masses. The Lake Kotokel record provides an example of complex interplay among several climatic/environmental controls of δ¹⁸O diatom during the Late Pleistocene and the Holocene.