The urokinase plasminogen activator system (uPAS) is an essential mechanism in a wide variety of biological processes such as fibrinoloysis, inflammation, atherosclerotic plaque formation, matrix remodeling during wound healing, tumor invasion, angiogenesis, and metastasis. The urokinase plasminogen activator (uPA) is a member of the urokinase plasminogen activator system (uPAS) which can bind to its receptor (uPAR) and initiates a proteolytic cascade resulting in the conversion of plasminogen to plasmin. Plasmin with its proteolytic function leads to degradation a number of extracellular basement membrane components as well as activation of metalloproteinases. This enzymatic function of uPA is involved in a range of physiopathological processes requiring basement membrane (BM) and/or extracellular matrix (ECM) remodeling, including tumor progression and metastasis. It has been frequently reported that the overexpression of uPA and its receptors is associated with tumour invasion and metastasis. Moreover, an increased expression of uPA, uPAR, and PAI-1is correlated with poor prognosis in several cancers including breast cancer. Therefore, due to the involvement of uPA in cancer progression, uPA system can be a potent candidate for manipulation and cancer treatment as a targeted therapy.