epigenetics is the study of heritable alterations in gene expression that are not accompanied by the corresponding change in DNA sequence. Three important epigenetic processes regulate gene expression at the level of chromatin including nucleosomal remodeling, DNA methylation, and histone covalent modifications. Chromatin is a highly dynamic structure composed of DNA and protein (histone and non-histone proteins). Histone amino-terminal regions can undergo modification by acetylation, methylation, phosphorylation, ubiquitylation, sumoylation and ADP ribosylation. The enzymes histone acetyl transferase (HAT) and histone deacetylase (HDAC) control the acetylation level of histones and thereby alter gene expression.Many cancers display molecular alterations that change the balance between HAT and HDAC activity. HDACs exert a pro‑oncogenic effect by silencing genes involved in differentiation, apoptosis and cell cycle arrest. Therefore, the inhibition of HDACs is a target for the development of novel anticancer therapy. Histone deacetylase inhibitors (HDACIs) show anticancer activity by promoting acetylation of histones. The effect of HDACI is different such as cell cycle arrest, inhibit DNA repair, and induce apoptosis.Photodynamic therapy is a form of radiation therapy that is composed of three important parts: a photosensitizer, molecular oxygen and light at a specified wavelength for producing reactive oxygen species (ROS), particularly singlet oxygen in tumor cells. The tumor cells would be destroyed by apoptosis and/or necrosis induced by ROS, achieving the goal of local treatment with minimum invasion.Although the role of photodynamic therapy on the epigenetic process such as DNA methylation and histone deacetylase is unknown, recently some studies demonstrated that the light could control epigenetic regulator such as HDAC enzymes. Eventually, a combination of photodynamic therapy with epigenetic may be a novel approach for a more tumor-selective treatment.