Hepatocytes rarely divide, but they have a unique capacity to reproduce in response to an appropriate stimulus, such as the removal of a portion of liver.This process involves controlled hyperplasia, or increased cell division, that usually restores the liver to within 5 to 10% of its original weight. Hepatic injury or partial removal leads to both systemic (e.g., in the blood and other tissues) and local (within the liver) release of growth factors that stimulate hepatocyte replication.

Because all hepatocytes can perform the necessary hepatic functions and all have an equal ability to replicate, the liver can undergo compensatory growth and restore its size. Liver regeneration plays an important role after surgical removal of a portion of liver (partial hepatectomy) and after injuries that destroy portions of the liver, such as viral, toxic, or ischemic damage. However, excessive damage can reach a "point of no return," and normal tissue will be replaced with scar tissue. The liver's ability to regenerate is also compromised by pre-existing or repeated liver damage or disease.