Liver cancer and diseases have become the leading cause of deaths in China. Liver diseases including liver failure and liver cancer can be genetic or caused by a variety of factors that damage the liver, such as viruses and alcohol overdose. However, the underlying mechanisms that maintain liver homeostasis remain unclear. Recent studies show that the Hippo signaling pathway plays a critical role in maintaining liver tissue homeostasis. Dysregulation of the Hippo signaling pathway impairs liver regeneration and remarkly enhances liver overgrowth and tumorigenesis. In this review, we summarize recent progresses on the roles and regulation mechanisms of the Hippo signaling pathway in liver development and diseases.