BACKGROUND: Cancer will become the leading cause of death worldwide in the 21st century, meanwhile, immunotherapy is the most popular cancer treatment method in recent years. COPI Coat Complex Subunit Beta 1 (COPB1) relates to human innate immunity. However, the role of COPB1 in pan-cancer remains unclear. OBJECTIVE: The purpose of this study was to explore the relationship between COPB1 mRNA expression and tumor infiltrating lymphocytes and immune examination sites in pan-cancer. METHODS: Data from multiple online databases were collected. The BioGPS, UALCAN Database, COSMIC, cBioPortal, Cancer Regulome tools, Kaplan-Meier Plotter and TIMER website were utilized to perform the analysis. RESULTS: Upregulation of COPB1 has been widely observed in tumor tissues compared with normal tissues. Although COPB1 has poor prognosis in pan-cancer, COPB1 high expression was beneficial to the survival of ESCA patients. Unlike ESCA, COPB1 expression in STAD was positively correlated with tumor infiltrating lymphocytes, including B cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Finally, we also found that the expression of COPB1 in STAD was positively correlated with PD-L1 and CTLA4. CONCLUSIONS: COPB1 may be a prognostic biomarker for pan-carcinoma, and also provide an immune anti-tumor strategy for STAD based on the expression of COPB1.