Congenital heart disease (CHD) is a type of birth defects due to the abnormal development of heart and blood vessels during embryonic stage. Studies indicate that the etiology of CHD is complicated. Genetic and epigenetic mechanisms including chromosomal abnormalities, gene mutations, nucleic acid modifications, non-coding RNAs may play important roles in CHD. At present, genetic mechanisms such as chromosome abnormality and gene mutation have been widely used in the diagnosis and treatment of clinical diseases. However, the application of genetic and epigenetic modification in diagnosis and treatment of CHD still need further research. This paper reviews the relationship between chromosomal abnormality, gene mutation, copy number variation, epigenetic modification and the occurrence of CHD, which may provide a basis for further exploring the early diagnosis and individualized therapy of CHD.