Abstract: Objective The presence of the mGlu5 in liver has been demonstrated, which plays significant roles during pathologic process of liver tissue. Our previous experiments showed that the agonist and antagonist of mGlu5 can affect the growth, apoptosis, invasion and migration in HepG2 cells, which suggested that mGlu5 may play a role in hepatocarcinogenesis. In this study, mouse primary hepatocytes and Hepa1-6 cell line were used to further understand the role of mGlu5 in hepatocarcinogenesis and its underlying mechanism. Methods Cell viability, the expression of mGlu5 and the signaling pathways were detected by MTT and Western blot assays respectively. Results mGlu5 was expressed both in Hepa1-6 cell line and in primary hepatocytes, but the expression was higher in the former. DHPG, which is the agonist of mGluI, activated mGluR5-mediated downstream ERK signal pathway, while no change in JNK or p38 signaling pathways was detected. We also found that activation of ERK signal pathway in the primary hepatocytes need higher concentration of DHPG. In addition, activation of mGlu5 can promote the cell viability of Hepa1-6 cell. Conclusion This study revealed that the expression and function of mGlu5 in mouse primary hepatocytes cell and in Hepa1-6 cell are different, which may be crucial in hepatocarcinogenesis.