Liver surgery is a process which induces various types of stress on the liver including the total occlusion of the blood inflow, hemorrhage, massive volume reduction, and postoperative infection. Animal studies have shown a gender dimorphic response of the liver for various stresses such as ischemia/reperfusion, hemorrhage/resuscitation, hepatectomy, portal branch ligation, and endotoxemia. Most of these studies demonstrated the female liver to be more tolerant under stressful conditions than the male liver. Estrogen, which is a representative female sex hormone, may be one of the responsible factors for this gender dimorphism. The mechanism of estrogen's salutary effect includes circulatory improvement, a reduced inflammatory response, a reduced oxygen radical production, and an improved hepatic regeneration. However, the clinical evidence that supports the results of these experimental studies is still insufficient. A well-controlled prospective clinical study is necessary to clarify the role of gender or sex hormone in the process of liver surgery. This may not only lead to a deeper understanding of the liver pathophysiology, but also to the possibility of hepatoprotective therapy using sex hormone modulators. This review summarizes the current understanding of gender dimorphism in the tolerance of the liver to various hepatic stresses, which occur during the process of major liver surgery.