Cancer development and progression is intimately related with post-translational protein modifications, e.g., highly reactive thiol moiety of cysteines enables structural rearrangements resulting in redox biological switches. In this context, redox proteomics emerge as a fundamental tool to identify and quantify redox-sensitive proteins and to understand redox mechanisms behind thiol modifications. Given the great variability in redox proteomics protocols, problems including decreased resolution of peptides and low protein amounts even after the enrichment steps may occur. Considering the biological importance of thiol’s oxidation in melanoma, we adapted the biotin-switch assay technique for melanoma cells in order to overcome limitations of the traditional method.