M Microbial life has adapted to various individual extreme conditions; yet, organisms simultaneously adapted to very low pH, high salt and high temperature are unknown. We combined environmental 16S/18S rRNAgene metabarcoding, cultural approaches, fluorescence-activated cell sorting, scanning electron microscopy and chemical analyses to study samples along such unique polyextreme gradients in the Dallol-Danakil area (Ethiopia). We identify two physicochemical barriers to life in the presence of surface liquid water defined by: i) high chaotropicity-low water activity in Mg 2+ /Ca 2+-dominated brines and ii) hyperacidity-salt combinations (pH~0/ NaCl-dominated salt-saturation). When detected, life was dominated by highly diverse ultrasmall archaea widely distributed across phyla with and without previously known halophilic members. We hypothesize that high cytoplasmic K +-level was an original archaeal adaptation to hyperthermophily, subsequently exapted during multiple transitions to extreme halophily. W We detect active silica encrustment/fossilization of cells but also abiotic biomorphs of varied chemistry. Our work helps circumscribing habitability and calls for cautionary interpretations of morphological biosignatures on Earth and beyond. Belilla et al. 3 Microbial life has adapted to so-called extreme values of temperature, pH or salinity, but also to several polyextreme, e.g. hot acidic or salty alkaline, ecosystems 1,2. Various microbial lineages have been identified in acidic brines in the pH range 1.5-4.5, e.g. in Western Australia 3,4 and Chile 3. However, although some acidophilic archaea thrive at pH~0 (Picrophilus oshimae grows at an optimal pH of 0.7) 5 and many halophilic archaea live in hypersaline systems (>30%; NaCl-saturation conditions), organisms adapted simultaneously to very low pH (<1) and high salt, and eventually also high temperature, are not known among cultured prokaryotic species 1. Are molecular adaptations to these combinations incompatible or (hot) hyperacidic hypersaline environments simply rare and unexplored? The Dallol geothermal dome and its surroundings (Danakil Depression, Afar, Ethiopia) allow to address this question by offering unique polyextreme gradients combining high salt content (33 to >50%; either Mg 2+ /Ca 2+ or Na + (/Fe 2+/3+)-rich), high temperature (25-110°C) and low pH (≤-1.5 to 6). Dallol is an uplifted (~40 m) dome structure located in the North of the Danakil depression (~120 m below-sea-level), a 200 km-long basin within the Afar rift, at the triple junction between the Nubian, Somalian and Arabian Plates 6. Lying only 30 km north of the hypersaline, hydrothermally-influenced, Lake Assale (Karum) and the Erta Ale volcanic range, Dallol does not display volcanic outcrops but intense degassing and hydrothermalism. These activities are observed on the salt dome and the adjacent Black Mountain and Yellow Lake (Gaet'Ale) areas 6,7 (Fig. 1a-b). Gas and fluid isotopic measurements indicate that meteoritic waters, notably infiltrating from the high Ethiopian plat...