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Background : Signal transducers and activators of transcription 3 (STAT3) and protein kinase substrate p36 may be involved in cell proliferation, differentiation and growth. Methods : Immunohistochemistry for STAT3 and p36 was performed in 46 patients with hepatocellular carcinoma (HCC). Results : STAT3 staining was present in the cytoplasm and/or nucleus, while p36 staining was present in the nucleus. STAT3 and p36 expression occurred in 78.3% (36/46) and 47.8% (22/46) of HCC patients, respectively. However, no correlation was found between STAT3 and p36 protein expression (p>0.05). Enhanced expression of STAT3 was negatively correlated with portal vein invasion (p=0.033). Expression of STAT3 in the nucleus was correlated with tumor grade (p=0.004). Enhanced expression of p36 was correlated with tumor grade (p=0.031). HCC was correlated with HBV infection (p=0.032). The patients’ 5- year survival was related to expression of p36 (p=0.044), but not to total STAT3 or nuclear STAT3 (p>0.05). Conclusions : The enhanced expression of STAT3 in the nucleus and the enhanced expression of p36 are associated with the aggressive phenotype of HCC. Enhanced p36 expression may contribute to poor survival of patients with HCC.