As a new promising therapeutical strategy for the treatment of liver diseases, gene therapy has drawn people's great attention. In gene therapy of hepatic diseases, it is critical to get therapeutic genes into hepatocyte for appropriate expression specifically. Over the past twenty years, receptor mediated gene delivery system have been extensively studied for liver-targeted gene delivery. However, non-viral gene delivery is still inefficient. This article reviewed the current non-viral vector used commonly, including their physicochemical properties, advantages and limitations, mechanisms of action for gene delivery, and applications modified for liver-targeted gene therapy, and the physical methods for hepatocyte gene delivery, such as electroporation and hydrodynamic injection. It also reviewed how to achieve optimal transfection efficiency.