Updated project metadata. Updated publication reference for PubMed record(s): 32561711, 31502396. We performed an in-depth proteome analysis of the haloarchaeal model organism Haloferax volcanii under standard, low and high salt and low and high temperature conditions using label-free mass spectrometry. Qualitative analysis of protein identification data from high pH/reversed phase fractionated samples indicated 61.1% proteome coverage (2,509 proteins), which is close to the maximum recorded values in archaea. Identified proteins matched to the predicted proteome in their physicochemical protein properties, with only a small bias against low molecular wright and membrane-associated proteins. Cells grown under low and high salt stress as well as low and high temperature stress were quantitatively compared to standard cultures by SWATH mass spectrometry. 2,244 proteins, or 54.7% of the predicted proteome, were quantified across all conditions at high reproducibility which allowed for global analysis of protein expression changes under these stresses. Pathway enrichment analysis by KEGG annotation showed that most major cellular pathways are part of H. volcanii’s universal stress response. In addition, specific pathways were found to be selectively affected by either salt or temperature stress.