Background: One important strategy during management of cancer is implementing a healthy diet regimn. Aim of the Work: The purpose of this work is to assess and explain the mechanisms of the ketogenic diet (KD) in cancer management via evaluation of the expression levels of Forkhead transcription factor O3a (FOXO3a), protein kinase B (AKT), and Phosphatase and tensin homolog deleted on chromosome ten (PTEN) genes in the Ehrlich ascitic carcinoma (EAC) model. Materials and Methods: The study involved 75 female mice which were divided into 5 groups: Group I (Negative control group) received intraperitoneal injections of saline and were fed a standard diet for 4 weeks. Group II (untreated (EAC)-bearing mice). Group III (mice bearing EACs received a KD on the day of tumor inoculation for 14 days). Group IV (mice bearing EACs received a KD for two weeks before and after tumor inoculation). Group V (ketone bodies control group) received a KD daily for 4 weeks. Results: The mean survival time of mice improved significantly in all groups fed the KD. KD treated groups showed a statistically significant increase in β-hydroxybutyrate (β-HB) levels and FOXO3a gene expression, along with a decrease in AKT gene expression compared to untreated group. However, KD treated groups showed a statistically significant increase in PTEN gene expression compared to untreated group. Conclusion: Based on these findings, the KD has evolved as a promising diet therapy in management of cancer, targeting the metabolism of cancer cells. Ketogenic diet significantly reduced cell viability through epigenetic impact.