The purpose of this study is to investigate the expression of epithelial membrane protein-3 (EMP3) in skin cutaneous melanoma (SKCM) and its correlation with clinical prognosis. The expression of EMP3 in SKCM and normal tissues was analyzed using GEPIA database. UALCAN database, TIMER database and GEPIA database were used to analyze the relationship between the expression of EMP3 and the prognosis of SKCM patients. The correlations between the expression of EMP3 and immune infiltration cells level and related markers of immune infiltration cells in SKCM were analyzed using TIMER database. The results showed that the expression of EMP3 in SKCM was significantly higher than that in normal tissues. The expression of EMP3 was not related to the overall survival rate of primary SKCM patients, whereas the high expression of EMP3 was significantly related to the lower overall survival rate of metastatic SKCM patients. The infiltration levels of B cells, CD4+T cells, CD8+T cells, neutrophils, macrophages, and dendritic cells were not associated with the prognosis of patients with primary SKCM, whereas the low infiltration levels of B cells, CD8+T cells, neutrophils, and dendritic cells were significantly associated with lower overall survival rate of patients with metastatic SKCM. The high expression of EMP3 in metastatic SKCM was significantly correlated with the lower infiltration levels of CD8+T cells, macrophages and neutrophils, and the lower expression of most markers of CD8+T cells and macrophages. This study suggests that the expression of EMP3 in metastatic SKCM is related to immune infiltration and clinical prognosis, which provides a theoretical basis for the diagnosis, treatment and prognosis evaluation of metastatic SKCM.