Background: The pituitary tumor-transforming gene 1 (PTTG1), also recognized as securin, plays a crucial role in diverse biological processes, such as restraining sister chromatid segregation, facilitating DNA repair, contributing to organ development, and governing angiogenesis. Additionally, it regulates the expression and secretion of transfer factors. The epigenetic characteristics of PTTG1 suggest its potential in elucidating the progression of malignant tumors in pan-cancer. Nevertheless, the current comprehension of this relationship remains limited, necessitating further comprehensive studies to delve into the underlying pathogenesis. Methods: This investigation aimed to explore the potential functions of PTTG1 in pan-cancer by leveraging existing databases, such as TCGA and GTEx. Notably, PTTG1 was overexpressed in nearly all tumors, indicating promising prognostic and diagnostic capabilities. Moreover, the observed correlation between PTTG1 and immune cell infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), and other immune features suggests its potential utility as a guide for immunotherapy. Results: The study unveils that the downregulation of PTTG1 expression in neuroblastoma results in reduced cell proliferation and increased apoptosis, substantiating the proposition that PTTG1 could serve as both a prognostic biomarker and a potential target for immunotherapy across various cancer types. Conclusions: This study centers on the exploration of the expression and role of PTTG1 in both tumors and the tumor microenvironment (TME), offering valuable insights for the development of cancer therapeutic strategies. These discoveries present potential alternative avenues for addressing clinically resistant cancers.