<h4>Objective</h4>To analyze the association between the <i>IRF5</i> gene variants rs3807135, rs3757385, and rs3778754 and mRNA expression levels in patients from western Mexico diagnosed with melanoma.<h4>Methods</h4>An analytical cross-sectional study was conducted including 374 individuals (153 patients with newly diagnosed melanoma and no previous treatment, and 221 controls). Here, IRF5 is linked to melanoma.