Background/Aims: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in the human population. Despite its significance, there is only limited understanding of pathological mechanisms and therapeutic options. Talin1, a focal adhesion complex protein that is required for cell adhesion and motility, regulates integrin interactions with extracellular matrix (ECM). In the present study, we aimed to study the possible role of Talin1 in diagnosis and prognosis of HCC. Methods: Expression of Talin1 protein was detected in normal liver tissues (n=10), HCC tissues (n=32) and adjacent non-cancerous tissues (n=32) by immunohistochemistry and real time PCR. Results: While Talin1 was observed in all tissues, the protein and mRNA expression of Talin1 in HCC tissues was significantly lower than that in the adjacent non-cancerous tissues and normal liver tissues(P<0.05). In addition, the expression of Talin1 in HCCs was significantly correlated with pathological differentiation, integrity of the tumor capsule, portal vein tumor thrombus and tumor size (P<0.05). Conclusions: Talin1 is possibly involved in the process of the carcinogenesis, infiltration and metastasis of HCC and has potential as a marker for diagnosis and prognostic assessment.