The sympathetic nervous system (SNS) infiltrates the liver and promotes hepatocarcinogenesis. A high density of sympathetic nerve fibers is associated with poor prognosis of hepatocellular carcinoma (HCC) patients. The SNS promotes the activation of Kupffer cells (KCs) via α1-adrenergic receptors in hepatocarcinogenesis. The SNS promotes hepatocarcinogenesis by modulating the activity of KCs and liver inflammation.