In this article, we aimed to explore the potential protective effect of curcumin against UV radiation-induced <i>DNMT1</i>, <i>DNMT3A</i>, <i>DNMT3B</i>, <i>HDAC5</i>, and <i>HDAC6</i> expression in immortalized keratinocytes (HaCaT), hepatocellular carcinoma (HepG2), and lung adenocarcinoma (A549) cells. The gene discussed is HDAC5; the disease is hepatocellular carcinoma.