Objective To investigate the expression and significance of TLR4、MyD88 and STAT3 in hepatocellular carcinoma.Methods S-P immunohistological assay were applied to detect the expression of TLR、MyD88 and STAT3 genes in 82 hepatocellular carcinoma tissues and adjacent normal tissues. Correlation analysis was used to determine the relation of TLR4、MyD88 and STAT3 with clinicopathological data.Result The positive rate of TLR、MyD88 and STAT3 expression was 76.8%、67.1% and 69.5% in 82 hepatocellular carcinoma tissues, significantly higher than the positive rate of 25.9%、12% and 8.5% in adjacent normal tissues (P<0.05). TLR4 expression was positively correlated with MyD88(r=0.612, P=0.011), STAT3(r=0.578, P=0.002), MyD88 and STAT3 expression was positively correlated (r=0.578, P=0.002). The expression of MyD88 and STAT3 in HCC is significant relation to gender, age, pathological grade, HBV infection and cirrhosis (P<0.05), but no significant relation to tumor size, venous infiltration (P>0.05) Conclusion TLR4、MyD88 and STAT3 protein are significantly over expressed in HCC tissues and promote the initiation and development of HCC by cell proliferation and immune escape.