Updated project metadata. Post-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of SLE. Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. We compared the Khib levels of SLE patients and healthy controls based on liquid chromatography-tandem mass spectrometry, and then performed proteomic analysis. The results showed that Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were further analyzed. Bioinformatics analysis showed that complement, coagulation cascade and platelet activation in immune-related pathways were significantly enriched, indicating that the differential modification proteins between them might affect SLE.