The major functions of Hippo (Hpo) signaling pathway are to control cell growth, proliferation, and apoptosis. As its important downstream player, yes-associated protein (YAP)-1 was originally found to promote cell proliferation and transformation. Overexpression of YAP-1 has been linked to tumor progression and worse survival in certain malignancies. However, it has been recently recognized as a tumor suppressor gene as well since it also induces apoptosis. Decreased or absent expression of YAP-1 is highly correlated with tumor progression and worse survival in other tumors such as breast cancer. It is clear that YAP-1 plays a dual role as oncogene and tumor suppressor gene in human oncogenesis, depending on the specific tissue type involved. Here, we reviewed the recent research on both the oncogenic and tumor suppressor function of YAP-1 and its significance in human malignancy. The clinical implication of YAP-1 expression in cancer prognosis and the development of targeted therapy will also be discussed.