Melanomas are tumors derived from melanocytes, which have high mortality and low treatment efficiency. Melanocytes are cells that produce the pigment melanin, which, under normal conditions, have the function of protecting the cell from possible damage caused by UV radiation, both by absorbing part of this radiation and by sequestering reactive oxygen species (ROS). However, many studies have shown that melanin in tumor cells may be related to processes of resistance to conventional treatments, especially photodynamic therapy. The process of melanin production (melanogenesis) in melanoma cells leads to a transient increase in ROS, which consequently induces several cellular modifications that allow the maintenance of cellular viability. Many studies on the effects generated by ROS in melanoma cells have been carried out, but little is known about the profile of proteins that undergo redox modification and that can act as signals in tumor survival. We investigated the profile of redox-modified proteins in murine melanoma cells with stimulated melanogenesis and submitted to rose bengal-photodynamic therapy (RB-PDT). A redox proteomics label-free approach based on the biotin switch assay technique with biotin-HPDP and N-ethylmaleimide (NEM) was optimized and used to assess the thiol-oxidized protein profile. Our results showed alterations that may affect biological processes, such as calcium signaling, translation, signal transduction, energetic metabolism, genomic stability, protein folding and trafficking, and stress response via redox signaling. The redox alterations observed in melanoma cells and identification of possible target proteins are of great importance to further understand tumor resistance mechanisms.