Stress-associated endoplasmic reticulum protein 1 (SERP1) is a gene induced by endoplasmic reticulum (ER) stress and a major contributor to multiple tumor types. Skin cutaneous melanoma (SKCM) is a highly aggressive and fatal cancer with poor treatment outcomes after progression. In this study, we evaluated SERP1's role in tumorigenesis, prognosis, and immune infiltration in SKCM. Patients with SKCM had low SERP1 expression. We identified differentially expressed genes between high- and low-SERP1 expression groups and conducted functional, pathway, and gene enrichment analyses. Protein-protein (PPI) and gene-gene interaction (GGI) networks were constructed via STRING and GeneMANIA, respectively. SERP1 mutation information was obtained through cBioPortal; location in the skin was identified through the Human Protein Atlas. Kaplan-Meier analysis revealed an association between low SERP1 expression and overall survival (OS), disease-specific survival (DSS), progress-free interval (PFI) rates, and worse prognosis in patients with multiple clinicopathological features. Cox regression analysis and nomograms further presented SERP1 level as an independent prognostic factor for patients with SKCM. Furthermore, there were significant correlations between SERP1 expression and immune infiltrates; thus, low SERP1 expression is associated with immune cell infiltration and can be considered a poor prognostic biomarker in patients with SKCM. Stress-associated endoplasmic reticulum protein 1 (SERP1) is a gene induced by endoplasmic reticulum (ER) stress and a major contributor to multiple tumor types. Skin cutaneous melanoma (SKCM) is a highly aggressive and fatal cancer with poor treatment outcomes after progression. In this study, we evaluated SERP1's role in tumorigenesis, prognosis, and immune infiltration in SKCM. Patients with SKCM had low SERP1 expression. We identified differentially expressed genes between high- and low-SERP1 expression groups and conducted functional, pathway, and gene enrichment analyses. Protein-protein (PPI) and gene-gene interaction (GGI) networks were constructed via STRING and GeneMANIA, respectively. SERP1 mutation information was obtained through cBioPortal; location in the skin were identified through the Human Protein Atlas. Kaplan-Meier analysis revealed an association between low SERP1 expression and overall survival (OS), disease-specific survival (DSS), progress-free interval (PFI) rates, and worse prognosis in patients with multiple clinicopathological features. Cox regression analysis and nomograms further presented SERP1 level as an independent prognostic factor for patients with SKCM. Furthermore, there were significant correlations between SERP1 expression and immune infiltrates; thus, low SERP1 expression is associated with immune cell infiltration and can be considered a poor prognostic biomarker in patients with SKCM.