Previous studies have shown that betatrophin is the potential regulator of triglyceride clearance [29], and was predicted able to block the catalytic site of LPL [36]. The silencing of betatrophin expression was significantly reduced circulating triglyceride and increased LPL activity and expression [25,37]. Moreover, patients with a higher level of betatrophin significantly correlated with a higher risk of nonalcoholic fatty liver disease (NAFLD) [38] and enhanced ER stress in hepatocyte [39]. Also, the higher expression of betatrophin was reported in patients with liver cirrhosis and has a significant association with the degree of liver fibrosis [40]. Our study was broadly consistent with previous findings that show the fundamental role of betatrophin in the pathogenesis of liver fibrosis related to fatty liver and metabolic syndrome. Thus, the alteration of liver and circulating betatrophin levels may enhance the early stage of hepatocellular carcinoma. According to the preliminary data, here the limitation of our study is that no clear information whether the alteration of betatrophin expression has a direct association with the silencing of miR-122 and early symptom of HCC. Furthermore, we cannot provide a comprehensive **data** the correlation of betatrophin with tumor growth factor that involved in liver fibrosis-HCC development. The result of this study suggests that this liver-derived hormone would also be beneficial as the potential biomarker for the hepatocellular carcinoma-linked metabolic syndrome. Moreover, these findings can contribute considerably to the IOP Conf. Series: Journal of Physics: Conf. Series 1146 (2019) 012003 IOP Publishing doi:10.1088/1742-6596/1146/1/012003 5 development of early diagnosis of HCC related to hypertriglyceridemia, fatty liver, and fibrosis associated obesity and metabolic perturbation. However, further extensive studies are necessary to support our hypothesis and establish the future contribution of betatrophin-miR122 in the pathogenesis of hepatocellular carcinoma caused by metabolic syndrome. The circulating betatrophin level and liver betatrophin expression may offer an opportunity for the clinical administration to prevent the severity of liver injury and patient mortality caused by hepatocarcinoma-related obesity.