Integrin beta-6 (ITGB6) is a subunit of the αvβ6 integrin heterodimer, which plays a crucial role in cell adhesion, migration, and signaling. ITGB6 is typically expressed at low levels in normal tissues but is significantly upregulated during tissue repair, inflammation, and in various cancers, including pancreatic, colorectal, and oral squamous cell carcinoma. Its overexpression is associated with tumor progression, metastasis, and poor prognosis, primarily through its interaction with extracellular matrix components like fibronectin and latent TGF-β, leading to TGF-β activation and subsequent promotion of epithelial-mesenchymal transition (EMT) and immune evasion. Due to its restricted expression in healthy tissues and strong association with aggressive cancer phenotypes, ITGB6 has emerged as a promising diagnostic biomarker and therapeutic target. Recent studies have explored the use of ITGB6-targeted antibodies, peptides, and imaging agents for cancer detection and treatment. However, further research is needed to fully elucidate its mechanistic roles and to develop safe and effective ITGB6-targeted therapies.