The development of cancer preventive drugs has undeniably revolutionized cancer treatment, offering hope and extending the survival of countless patients. However, it is essential not to overlook the potential side effects of these drugs, alongside their potent therapeutic effects. One of the primary adverse effects of anti-cancer drugs is hepatotoxicity. Drug-induced liver injury (DILI) is a leading cause of hepatotoxicity, and it sometimes proves challenging to manage, even leading to the discontinuation of the medication. This chapter will address the effects of anti-cancer drugs on the liver and the mechanisms associated with DILI, while also focusing on emerging strategies to reduce the risk of DILI.