The mechanism by which TMEM59L regulates tumorigenesis and cancer pathophysiology remains unclear, but the relationship we observed between TMEM59L and the hallmarks of cancer could improve our understanding of the functional roles of TMEM59L. GSEA analysis demonstrated that TMEM59L expression was strictly linked with hallmarks of malignancy and immune-related pathways in most cancers, such as EMT, P53, apoptosis, cell cycle, WNT, IL-6-JAK-STAT3, IL2-STAT5 and TGF-β signaling pathways. Here, TP53 is linked to cancer.