Sertraline reduced melanoma cell viability, colony formation, and migration in vitroSignificantly downregulated TCTP expression, leading to increased P53 levelsInduced apoptosis in melanoma cells (increased Caspase‐3, decreased Ki67)Inhibited tumor growth more effectively than DTIC in a murine melanoma modelFindings suggest sertraline may be repurposed as an anti‐melanoma therapy targeting TCTP. This evidence concerns the gene TP53 and melanoma.