Hepatocellular Carcinoma (HCC) is the fourth leading cause of cancer-related death in the World. Epidermal Growth Factor Receptor (EGFR) pathway plays an important role in HCC tumorigenesis. In the tumor microenvironment of HCC, the expression of EGF is aberrant. Here we describe the EGF-dependent regulation of URGCP gene in Human Hepatoma cancer cells (Hep3B). The effect of EGF cytokine on Hep3B proliferation was shown using MTT method. EGF-mediated URGCP expression was determined at mRNA and protein level with qRT-PCR analyses and Western blotting method, respectively. Different lengths of URGCP promoter constructs were transient transfected in to Hep3B cells and the basal promoter activities were determined in the presence of EGF. In addition, some pathway analyses were performed to find out the mechanism of EGF mediated up-regulation of the URGCP gene. In the presence of EGF, URGCP expression increases in concentration and time dependent manner. EGF mediated URGCP up-regulation might depend on a cis-acting element located between -344 and -482 positions in its promoter.