Epigenetics, the study of heritable changes in gene expression without alterations to the underlying DNA sequence, is pivotal in understanding cancer development and progression. This special issue delves into the intricate mechanisms governing epigenetic modifications, particularly focusing on histone modification and DNA methylation, and their profound implications in cancer biology. Histone modifications, encompassing a spectrum of chemical alterations to histone proteins, dynamically regulate chromatin structure and gene expression. Perturbations in histone modifications, along with aberrant DNA methylation patterns, are intricately linked to oncogenesis, influencing key cellular processes such as proliferation, differentiation, and apoptosis. Through a series of comprehensive reviews and original research articles, this special issue sheds light on the diverse landscape of histone modifications and DNA methylation in cancer, elucidating their roles in driving tumorigenesis and identifying potential therapeutic targets. The interplay between histone modifications and DNA methylation provides further insights into the complex epigenetic mechanisms underlying cancer development, offering potential avenues for diagnostic and therapeutic advancements in various cancer types.