Abstract: Objective：To investigate the role and molecular mechanism of Na+/Ca2+ exchanger 1 (NCX1) in the invasion and proliferation of hepatocellular carcinoma (HCC), and to provide new therapeutic targets for the clinical diagnosis and treatment of hepatocellular carcinoma.Methods：Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect NCX1 mRNA and protein expression in different HCC cell lines. Lentiviral vectors pGC-SIL-GFP-shRNA-NCX1 and pGC-FU-GFP-NCX1 were constructed and transfected into hepatoma cells. Cell migration and invasion experiments were used to observe the effect of NCX1 on the migration and invasion of HCC cells; cell proliferation assay was used to observe the effect of NCX1 on the proliferation of hepatoma cells; Western blotting and ELISA were used to detect the expressions of NCX1-related proteins.Results：The expression of NCX1 in high metastatic potential HCC cell lines (MHCC97H, HCCLM3) was higher than that of low metastatic potential HCC cell lines (HepG2, Huh7, SMMC-7721), and the difference was statistically significant (P<0.05). After transfection of NCX1, the invasion and proliferation ability of HCC cells increased significantly (P<0.05); the secretion of cytokines (TGF-β 1, IL-6 and TNF- α) increased significantly (P<0.05); the expressions of epithelial-mesenchymal transition (EMT) related proteins in HCC cells were significantly increased (P<0.05).Conclusions：NCX1 can promote the growth, invasion and metastasis of hepatocellular carcinoma by increasing the expressions of EMT-related proteins in HCC cells, and it is a potential target for the diagnosis and treatment of liver cancer.