Hepatocellular carcinoma (HCC) is an aggressive malignant tumor and the third leading cause of cancer-related mortality worldwide. Transmembrane channel-like protein 8 (TMC8) is reported to play a major role in several aspects of human pathophysiology, such as ion channel permeability, human papillomavirus infection and skin cancer; however, its role in HCC has not been fully elucidated. The aim of the present study was to investigate the expression levels of TMC8 in 146 pairs of liver cancer samples and adjacent non-tumorous samples using immunohistochemistry. Reverse transcription-quantitative polymerase chain reaction analysis was used to confirm the results. The association between TMC8 expression and clinicopathological characteristics, including overall survival, was analyzed. The results indicated that the expression of TMC8 was significantly upregulated in HCC tissues and associated with metastasis and hepatitis B virus infection. According to the analysis of the overall survival using Cox proportional hazard regression model, higher expression of TMC8 was associated with a poorer prognosis and the over-expression of TMC8 was an independent risk factor for HCC. By contrast, HBsAg did not significantly affect the survival of HCC patients. These results suggest that the over-expression of TMC8 in HCC predicts poor prognosis and may be a potential biomarker for this type of cancer.