Hepatic ischemia-reperfusion injury is a complicated systemic process that affects several tissues and organs in addition to being a pathologic process that affects the liver. Several studies have shown that hepatic reperfusion severely impairs liver function. That also produces irreversible damage that causes dysfunction of many organs. The regulation of hepatic ischemia-reperfusion injury (IRI) is influenced by various factors, such as mitochondrial damage, anaerobic metabolism, intracellular Ca2+ overload, oxidative stress and ROS production, and chemokines as well as cytokines generation. Most of the cytokines are generated by helper T cells and neutrophils. A target of Matrix Metalloproteinases (MMPs) in chronic and acute liver injury caused by ischemia can be a significant facilitator of early leukocyte recruitment. Neutrophil gelatinase-associated lipocalin (NGAL) and MMPs could be employed as indicators of the severity of ischemia-reperfusion (I-R) injuries. This review examines the relationship between the components of hepatic IRI, MMPs, and the available pharmaceutical treatments for this condition.