Objective To investigate the expression level of Fc receptor-like protein 3 (FCRL3) in hepatocellularcarcinoma and to determine its effect on the proliferation and migration of hepatocellular carcinoma HepG2 cells. MethodsThe expression of FCRL3 mRNA and protein was detected in hepatocellular carcinoma tissues, healthy liver tissues, andHepG2 cells by RT-PCR. The effects of FCRL3-specific small interfering (si)RNA on the proliferation and migration ofHepG2 cells were detected by an MTT assay and cell scratch test. Results FCRL3 mRNA and protein expression wassignificantly higher in hepatocellular carcinoma tissues than in healthy liver tissues ( P <0. 05). FCRL3 mRNA and proteinexpression levels were significantly lower following siRNA in HepG2 cells, and the proliferation rate and migration abilitywere significantly decreased ( P < 0. 05). Additionally, the expression of FCRL3 mRNA and protein in HepG2 cellsoverexpressing FCRL3 was significantly increased compared with controls, as well the proliferation rate and migrationability ( P <0. 05). Conclusions The expression of FCRL3 in hepatocellular carcinoma is up-regulated compared withhealthy liver tissue. FCRL3 inhibition reduces the proliferation and migration of hepatoma cells, suggesting that FCRL3 plays an important role in the progression of hepatocellular carcinoma.