Cutaneous squamous cell carcinoma (CSCC) is a kind of malignant tumor originated from keratinocytes within the epidermis and its appendages. Its etiology and pathogenesis are complex and unclear. The incidence of CSCC is increasing in the whole world, which makes the research on its pathogenesis increasing day by day. Epigenetics does not change genome sequence, but regulates gene expression by DNA methylation, histone modification, noncoding RNA, chromatin remodeling and so on. Its reversible and stable genetic characteristics will provide a new idea for the study of pathogenesis of CSCC.