Background: Hepatocellular carcinoma is the most frequent primary malignancy of the liver. It is the sixth most common cancer and third most frequent cause of cancer-related death worldwide. Objective: Epigenetic mechanisms (such as methylation, acetylation, and ubiquitination) are altered in HCC. One of these epigenetic mechanisms is Histone acetylation. The balance between histone transacetylases and deacetylases is often damaged in cancer, leading to changed expressions of tumor suppressor genes and/ or proto-oncogenes. Methods: HepG2 cells were treated with curcumin, valproic acid and curcumin + valproic acid than subjected to MTT assay, DNA fragmentation and real time PCR. Results: The result from MTT assay showed that IC50 of curcumin = 0.91 mM, valproic acid = 2.61 mM, curcumin + valproic acid = 1.12 mM. Real time PCR showed decrease in HDAC1, VEGF, IL- 6 and increase in PTEN, P53 genes expression in cell treated with curcumin or valproic acid individually while treatment of both show no synergism