Granulin-epithelin precursor (GEP) is a novel growth factor whose up-regulation we previously reported in 72% of hepatocellular carcinoma (HCC). GEP expression has been reported to be associated with p53 protein accumulation in a breast cancer study, though the p53 mutation status was not revealed. We aim to investigate whether p53 protein and mutation status correlates with GEP expression in HCC. The statistical comparison of p53 and GEP data revealed an overall positive association between the two protein expression patterns (P<0.001). Upon detailed analysis, the association of p53 and GEP protein expression was found to be highly significant only in HCCs with wild-type p53 (P=0.001); there was no association in HCCs with p53 mutation (P=0.669). The GEP levels in the HepG2 hepatoma cell line with a wild-type p53 background were modulated by transfection experiments. Overexpression of the GEP protein resulted in an increased p53 protein level and suppression of the GEP protein resulted in a decreased p53 protein level in HepG2 cells. In summary, we demonstrated that p53 wild-type protein nuclei accumulation is associated with GEP protein expression in human HCC specimens, and GEP modulates p53 wild-type protein levels in vitro.