Epigenetic alterations in cancer play a variety of roles. Aberrant DNA methylation, as one of the epigenetic mechanisms, has been widely studied in both tumor and liquid biopsies and provide a useful bench mark for treatment response in cancer. Recently, several studies have reported an association between the type of diet and epigenetic modifications. Whereby there is a growing interest in finding the "anti-cancer diet formula", if such a thing exists. In this sense, ketogenic diets (KD) have reported potentially beneficial effects, which were able to prevent malignancies and decrease tumor growth. Some studies have even shown increased survival in cancer patients, reduced side effects of cytotoxic treatments, and intensified efficacy of cancer therapies. Although the biological mechanisms of KD are not well understood, it has been reported that KD may affect DNA methylation by modulating the expression of crucial genes involved in tumor survival and proliferation. However, there are many considerations to take into account to use ketotherapy in cancer, such as epigenetic mark, type of cancer, immunological and metabolic state or microbiota profile. In this review, we argue about ketotherapy as a potential strategy to consider as coadjuvant of cancer therapy. We will focus on mainly epigenetic mechanisms and dietary approach that could be included in the current clinical practice guidelines.