Liver regeneration is a process in which the liver recovers its mass and function after injury due to various causes such as hepatectomy, virus infection and intoxication. This regeneration invokes a series of complex processes which may involve the actions of various cytokines, cell proliferation and cell growth. In response to cytokine stimuli, receptor-mediated signaling systems are activated, and many proteins are transcriptionally up-regulated to increase liver mass and improve liver function. In this review, we focus on the roles of signal transducer and activator of transcription-3 (STAT3) and its functions in mitogenic and other responses during liver regeneration following hepatectomy. We also describe newly discovered target genes of STAT3 and discuss their potential roles in liver regeneration after injury due to various causes.