Hydrogen sulfide (H₂S) is an endogenous gasotransmitter implicated in the regulation of protein function. To investigate changes in global protein abundance associated with exogenous H₂S exposure, EA.hy926 cells were treated with 60 μM NaHS or vehicle and analyzed by data-independent acquisition (DIA) proteomics. This dataset contains the proteomics data comparing NaHS-treated cells with vehicle-treated controls and was generated as part of a study investigating H₂S-associated regulation of HDAC6-dependent protein deacetylation and endothelial function.