Objective To investigate the effect of high mobility group leucine-rich repeats and immunoglobulin-like domain1 gene(LRIG1) on the proliferative activity of human hepatoma cell line Hep-G2 in vivo and in vitro and its potential action mechanism.Methods The Hep-G2 cells,cultured for 24 h by DMEM supplemented with 10% fetal bovine serum (FBS),were treated with none,pEGFP-N1 and pEGFP-N1-LRIG1.Cell proliferation was observed by cell counting kit-8 (CCK-8) analysis.Transwell invasion assay was used to monitor the changes of Hep-G2 cell malignant phenotypes.Changes of LRIG1 and epidermal growth factor receptor (EGFR) expression at mRNA and protein levels were measured by realtime polymerase chain reaction (PCR) and Western blotting,respectively.Results The absorbance (A) values at 24,48 and 72 h in control group,pEGFP-N1-LRIG1 group and pEGFP-N1 group were 0.968 ±0.050,0.924±0.070,0.552 ±0.060; 0.975±0.120,0.864 ±0.200,0.509±0.130; 0.983 ±0.180,0.803 ±0.140,0.465 ±0.230.As compared with control group and pEGFP-N1 group,proliferation of Hep-G2 cells was significantly inhibited in pEGFP-N1-LRIG1 group (P < 0.05).The number of invasive cells in pEGFP-N1-LRIG1 group,control group and pEGFP-N1 group was (6.24 ± 1.52),(15.19 ± 1.32) and (14.85 ± 1.24),respectively.As compared with control group and pEGFP-N1 group,the invasive ability of Hep-G2 cells was significantly inhibited in pEGFP-N1 group (P < 0.05).LRIG1 could significantly suppress the expression of epidermal growth factor receptor (EGFR) mRNA and protein in Hep-G2 cells in vitro (P < 0.05).Conclusion LRIG1 could promote malignant phenotypes of Hep-G2 cells probably by inhibiting the expression of EGFR mRNA and protein. Key words: Carcinoma, hepatocellular; Epidermal growth factor receptor; Phenotypes