Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and occurs more often in men than in women; however, little is known about its underlying molecular mechanisms. The present study investigated the effect of estrogen receptor (ER)α and ERβ on peroxisome proliferator-activated receptor γ (PPARγ) expression in Hep3B cells. We examined PPARγ, ERα and ERβ mRNA and protein expression by RT-PCR and western blotting. In order to determine whether PPARγ plays a central role in HCC, we screened for PPARγ expression in liver cancer patient tissues and differentially differentiated HCC cell lines (HA22T, Huh-7, Hep3B and HepG2). We found that PPARγ expression was highly expressed in liver cancer tissues and in Hep3B cells. Furthermore, overexpression of ERα and ERβ was found to decrease PPARγ expression at the transcriptional as well as at the translational level in a ligand-dependent manner. In summary, the present study demonstrated that both ERα and β were sufficient to inhibit PPARγ and provide a valuable therapeutic option for the treatment of HCC patients.