Worldwide, hepatocellular carcinoma (HCC) is one of the human cancers with a high mortality rate despite its early diagnosis in patients and improvements in therapeutic technology. HCC accounts for up to 90% of all primary liver cancers and represents a major health problem 1,2 . Chronic infection by hepatitis B and C and chronic alcohol consumption are major causes, as well as metastasis from tumors elsewhere in the body. Because only 10-20% of liver cancers can be surgically removed, the prognosis for the disease is very poor 3 . The cumulative 3-year recurrence rate remains high, approximately 80% after resection with a curative aim, and usually results in a high rate of mortality 4 . Moreover, most HCC exhibit resistance to conventional chemotherapeutic agents. Therefore, the development of an effective HCC treatment strategy remains an unmet medical need 5 . Accordingly, researchers have aimed to derive target genes and drug candidates for HCC; however, the development of targeted drugs has not yet significantly improved outcomes 5,6 . Lately, the paradigm in cancer biology has shifted from the study of the genetics of tumor cells alone to the complicated crosstalk between cancer and the tumor microenvironment (TME) [7][8][9] . The TME is the cellular environment in which the tumor exists, including the surrounding blood vessels, immune cells, fibroblasts, other cells, signaling molecules, and the extracellular matrix (ECM). Recent studies have shown that the stromal cells in HCC have a dynamic and flexible function in

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