S-Nitrosoglutathione (GSNO) is an intracellular redox signaling molecule, also implicated in nitrosative stress. GSNO actions include modifications of Cys thiols in proteins. In this study, we focused on a GSNO reaction with a Cys4 zinc finger (ZF) sequence of human protein XPA, crucial to the nucleotide excision repair pathway of DNA repair. By using a corresponding synthetic 37-residue peptide acetyl-DYVICEECGKEFMDSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) and combining the detection of noncovalent and covalent complexes by ESI-MS with zinc release monitored by the zinc-sensitive chromophore 4-(2-pyridylazo)resorcinol (PAR), we demonstrated that the reaction of XPAzf with GSNO yielded S-nitrosylated intermediates, intrapeptide disulfides, and mixed glutathione disulfides. The reaction started with the formation of a complex of GSNO with ZnXPAzf followed by thiol transnitrosylation reactions and the final formation of disulfides. The results obtained suggest that at low levels/transient exposures, GSNO may act as a reversible regulator of Cys4 ZF activity, whereas transnitrosylation by GSNO, occurring at prolonged exposures, may cause deleterious effects to the functions of Cys 4 ZF proteins. In the case of XPA, this may lead to DNA repair inhibition.