Although medicine has made unprecedented advancements over the last decades, hepatocellular carcinoma (HCC) is still a major unsolved problem. Despite the great progress that has been achieved in respects of exploring the risk factors, molecular characteristics and epidemiology of HCC, there is still a lack of effective means to HCC. With the deepening of research on HCC, hepatic stellate cells (HSCs) have been demonstrated to play a key role in the pathogenesis, development and prognosis of HCC. Here, the authors address HSCs in terms of it regulating HCC through direct and indirect ways, and the prevention and treatment of HCC by targeting the abilities of HSCs.