Colorectal cancer (CRC), a multi-step, multi-factor complex disease, is a common malignant tumor of the digestive tract. It has become the world’s third most common cancer and the second most common cause of death from cancer 
. Both genetic and environmental risk factors play essential roles during the development of CRC 
. In recent years, there have been large advances in cancer diagnosis technology. However, because the early symptoms are not dominant, most patients are diagnosed at an advanced stage, which affects the prognosis. Therefore, it is urgent to reduce the high incidence and mortality of CRC, and to develop advanced prevention and treatment strategies. For decades, people have elucidated many aspects of CRC biology, including genetics, epigenetics, metabolism and signaling pathways. Among them, epigenetic changes and cellular metabolic reprogramming play a key role in the occurrence and development of CRC, which is becoming more and more important.
Epigenetics refers to the regulatory code that dictates gene expression or not and can be stably inherited in the absence of a constant genomic sequence. The current research content of epigenetics mainly includes DNA methylation and hydroxylmethylation, histone modifications, chromosome remodeling, and non-coding RNA regulation. In the early stage of CRC, DNA methylation status begins to change abnormally, mainly through the hypermethylation of some CpG islands leading to the down-regulation of gene expression and genome-wide hypomethylation, which cause genome instability to participate in tumorigenesis and development 
. Histone modifications are often closely related to DNA methylation and act together in the process of gene transcription. Covalent modifications in histones includes acetylation, methylation, phosphorylation, ADP-ribosylation, ubiquitination, succinylation and myristoylation, etc. Histone methylation modifications mainly include the monomethylation, dimethylation or trimethylation of histone H3 or H4, such as H3K4me2, H3K4me3, H3K9me3 and H3K27me3. Histone acetylation modifications mainly include histone H3 and H4 acetylation. Histone modification significantly affects gene expression; therefore, there are obvious histone modification abnormalities in CRC 
. MicroRNA (miRNA) is a small single-stranded non-coding RNA that can regulate the expression of various oncogenes and tumor suppressor genes after transcription. The dysregulated expression of many miRNAs has been shown to mediate important signaling pathways in the multi-step carcinogenesis of CRC 
. In recent years, long non-coding RNA (lncRNA) has also been shown to be highly associated with the tumorigenesis of CRC 
. Even in mitochondrion, epigenetics also plays a fundamental role in energy hemostasis 
Cell division and proliferation requires a large amount of protein, lipid and nucleic acid as molecular raw materials and adenosine triphosphate (ATP) as energy, leading to the reorganization of anabolic flow in tumor cells. Metabolic reprogramming contributes to tumor progression and metastasis, which is considered to be an important hallmark of cancer 
. The most dominant metabolic reprogramming is the aerobic glycolysis, also called the Warburg effect. Tumor cells increase glucose consumption to promote glycolysis, converting pyruvate to lactic acid even under aerobic conditions, which is different to that of the normal cells. However, glutamine metabolism and oxidative phosphorylation (OXPHOS), as well as lipometabolism and one-carbon pathways, are also altered in some tumor cells because of genetic heterogeneity and microenvironmental discrepancy 
. Cellular metabolism is exquisitely modulated. Nonetheless, the regulatory axis in tumors are usually disorganized. This is the reason why dysregulated cell metabolism is observed in tumors. Cell metabolism is one of the essential factors contributing to carcinogenesis, and is also a result of malignancy 
. Studies have found that metabolic reprogramming is widespread in CRC. In different types of cancers, including CRC, dysregulated metabolic pathways such as abnormal glycolysis, glutamate and lipid synthesis are often observed, leading to unlimited tumorigenesis 
It is worth noting that certain metabolic changes are known to occur at the epigenetic level, so that epigenetics and metabolism are highly intertwined in a mutually beneficial manner 
. Metabolites produced in metabolic pathways, such as glycolysis cycles and OXPHOS, can be used as cofactors for epigenetic regulation 
. Studies have also shown that epigenetics can regulate the expression of metabolism-related genes and affect the metabolic reprogramming of tumor cells 
. Since many metabolic changes and epigenetic regulation are common in multiple cancer types, they become promising targets for tumor therapy. The purpose of this review is to describe the interactions between epigenetic changes and metabolic reprogramming, and to list the research progress of drugs targeting epigenetics and metabolism in CRC.