Background: Skin Cutaneous Melanoma (SKCM) is the deadliest cutaneous neoplasm. Previous studies have proposed ubiquitin-like protein FAT10 plays key roles in the initiation and progression of several types of human cancer, but little is known about the interrelation between FAT10 gene expression, tumor immunity, and prognosis of patients with SKCM.Methods: Here, we first performed pan-cancer analysis for FAT10’s expression and prognosis using the Cancer Genome Atlas and the Genotype-Tissue Expression data. Subsequently, we investigated the mRNA expression level, prognostic value, and gene-gene interaction network of FAT10 in SKCM using the Oncomine databases, GEPIA, TIMER, UALCAN, and starBase. The relationship between FAT10 expression and tumor immune invasion was studied by using the TIMER database. Additionally, the expression and functional status of FAT10 in SKCM were evaluated by the single-cell RNA sequencing and CancerSEA databases.Results: In this study, we found that FAT10 expression was increased in SKCM and was correlated with a better survival rate in patients with SKCM. Moreover, we identified FAT10 level was significantly positively associated with immune infiltrates, biomarkers of immune cells, and immune checkpoint expression, and negatively correlated with tumor cell invasion and DNA damage, indicating that increased FAT10 expression in SKCM was a favorable response to immune checkpoint inhibitors.Conclusion: Our findings suggest that upregulation of FAT10 correlated with better prognosis and tumor immune infiltration in SKCM.