The TOB1 gene, mapped on 17q21, is a member of the BTG/Tob family. In breast cancer it has been identified as a candidate tumor suppressor gene. However, whether TOB1 is a bona fide tumor suppressor and downregulated in hepatocellular carcinoma (HCC) remains unclear. In addition, whether its expression is regulated through methylation requires investigation. In the present study, we therefore analyzed the expression of TOB1 in HCC and its methylation levels in human HCC and breast cancer. No significant difference in the expression levels of TOB1 was observed between tumor tissues and adjacent normal tissues in HCC. Quantitative methylation analysis by MassArray revealed no significant differences at single CpG sites or in the global promoter region, and all these CpG sites shared a similar methylation pattern in HCC and breast cancer. Moreover, 5-aza-2'-deoxycytidine treatment of three tumor cell lines did not cause elevation of TOB1 mRNA in HepG2 cell lines. Based on these data, we speculate that TOB1 may be a candidate non-tumor suppressor gene in HCC. Furthermore, the clinical outcome was not correlated with TOB1 expression or expression rate. In addition, TOB1 expression or expression rate was not correlated with the overall survival (OS) rates or cumulative recurrence rates. Taken together, we suggest that TOB1 does not act as a tumor suppressor in HCC.