Objective:This paper focus on the correlation and clinical pathological significance of toll-like receptor 3(TLR3) and its signal molecules TIR-domain-containing adaptor protein including IFN-β (TRIF) and autophagy related gene,LC3 and Beclin 1,expressions in human hepatocellular carcinoma (HCC),and its relevant mechanism. Methods:We collected and followed-up 101 cases of HCC cases,and built tissue microarray. HE staining for HCC tissue differentiation and immunohistochemical staining were performed to detect the expression of Ki-67 (cell proliferation marker),TLR3,TRIF,LC3 and Beclin 1,respectively. TUNEL was performed to detect the apoptotic signals of cancer cells. Statistical analysis was performed to analyze its correlation with cancer clinical pathological factors and prognosis. Results:In HCC,the expressions of TLR3 and TRIF were positive correlated(ρ=0.640,P < 0.001). Its high expression was positively correlated with HbsAg infection,cirrhosis background,cell apoptosis index(AI) and total 5-year survival rate,and negatively correlated with cancer cell proliferation,vascular invasion,Edmondson grading and TNM staging. Beclin1 and LC3 expression was significantly positive correlated(ρ=0.587,P < 0.001). Both high expressions were respectively positively correlated with vascular infiltration,Edmondson grading,TNM staging and cancer cell proliferation,but negatively correlated with apoptosis index(AI) and 5-year survival rate(P < 0.001). TLR3 and TRIF respectively negatively correlated with the expression of LC3 and Beclin 1(both P < 0.001). Conclusion:The expressions of TLR3 and signaling molecules TRIF,cell autophagy related gene Beclin1 and LC3 respectively influence the biological behavior and prognosis of HCC by regulating cell proliferation,apoptosis and autophagy. There are cross points existing between Beclin1 mediated autophagy pathway and TLR3 mediated apoptosis pathway in HCC. Abnormalities of the two pathways may be one of the mechanisms in HCC occurrence and progress.