Acute liver failure (ALF) usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate. Hepatic stellate cells (HSCs) are famous for their role in liver fibrosis. Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF, the accurate mechanism is still not fully understood. This review focuses on the recent advances in understanding the functions of HSCs in ALF and revealed both protective and promotive roles during the pathogenesis of ALF: HSC activation participates in the maintenance of cell attachment and the architecture of liver tissue via extracellular matrix production and assists liver regeneration by producing growth factors; and HSC inflammation plays a role in relaying inflammation signaling from sinusoids to parenchyma via secretion of inflammatory cytokines. A better understanding of roles of HSCs in the pathogenesis of ALF may lead to improvements and novel strategies for treating ALF patients.