The blood-brain barrier (BBB) serves as a critical protective mechanism for the central nervous system (CNS), controlling the selective passage of molecules between the brain and the bloodstream. Claudin proteins, key components of tight junctions, play a central role in maintaining BBB integrity and regulating its permeability. Recent research has increasingly focused on how Claudins contribute to brain metastasis, where tumor cells alter Claudin expression to breach the BBB and invade brain tissue. While Claudin family such as Claudin-1 and Claudin-5 are essential for maintaining BBB function, their dysregulation in tumor cells facilitates BBB disruption, promoting metastasis. This review explores the dual role of Claudins in tumor progression, detailing how they regulate BBB permeability and enable tumor cells to cross the barrier. Additionally, we discuss the potential of Claudin proteins as therapeutic targets in cancer treatment, offering new insights into mechanisms of brain metastasis.