Endothelial dysfunction is regarded as an early key event in multiple diseases. The assessment of vascular nitric oxide (NO) level is an indicative of endothelial dysfunction. In liver cirrhosis, on one hand, endothelial dysfunction is known as impaired endothelium-dependent relaxation in the liver microcirculation and contributes to increased intra-hepatic vascular resistance, leading to portal hypertension. On the other, increased production of vasodilator molecules mainly NO contributes to increased endothelium-dependent relaxation in the arteries of the systemic and splanchnic circulation. The aims of this review are to summarize and discuss: (1) unique characteristics of sinusoidal endothelial cell (SECs) and SEC dysfunctions in cirrhosis, and (2) endothelial dysfunctions in the arterial splanchnic and systemic circulation in cirrhosis with portal hypertension.