Aim:To investigate the effect of CX3CR1 on the proliferation migration and invasion abilities of hepatocellular carcinoma(HCC) cell lines and its mechanism. Methods:The expression of CX3CR1 at mRNA and protein levels of 7721,HepG2 and human normal liver epithelial cells LO2 was detected by Q-PCR and Western blot. The 7721 cells were transfected with the overexpression plasmid of CX3CR1;the HepG2 cells were transfected with siRNA of CX3CR1,and the expression of CX3CR1 at mRNA and protein levels were detected by Q-PCR and Western blot. The cell proliferation ability was detected by MTT and clone formation assay. The migration and invasion ability were detected by Wound-healing and Transwell assays. The protein levels of PI3K/AKT and MAPK/ERK were detected by Western blot. Results:The expression of CX3CR1 was lower in 7721 cells than that in HepG2 cells. After overexpression plasmid was transfected into 7721 cells,the expression of CX3CR1 was up-regulated; cell proliferation migration and invasion abilities were increased. Meanwhile, the levels of p-ERK and p-AKT were up-regulated. After siRNA was thansfected into HepG2 cells,the expression of CX3CR1 was down-regulated,and cell proliferation, migration and invasion abilities were decreased, with the levels of p-ERK and p-AKT down-regulated. Conclusion:CX3CR1 can promote the proliferation, migration and invasion abilities of hepatocellular carcinoma(HCC) cells. The activation of PI3K/AKT and MEK/ERK signaling pathway may play an important role in these processes.