Objective To investigate the expression of LGR5 in human hepatocelluar cancer tissues and four human liver cancer cell lines and to evaluate its value in the development of hepatocellular cancer.Methods The mRNA and protein expression of LGR5 in human liver cancer cell lines and normal liver cell were detected by real-time PCR and Western blotting. Expression of LGR5 and β-catenin in hepatocellular cancer tissue was determined by immunohistochemistry. LGR5 localization and expression in HepG2 cells were tested by immunocytochemical staining. Results Western blotting and real-time PCR results demonstrated that the expression of LGR5 decreased significantly in HepG2, Hep3B, Huh7 and PLC cells compared to LO2 cells(EM>P/EM> <0.05). Immunohistochemistry results also showed that LGR5 was downregulated in cancer tissue compared to adjacent tumor tissue, whereas β-catenin expression was upregulated in cancer tissue. Conclusion Compared to adjacent tumor tissue and normal liver cells, LGR5 expression was significantly downregulated in 36 cases of hepatocelluar cancer tissues and four kinds of h