Existing evidence has demonstrated that epigenetic modifications (including DNA methylation, histone modifications, and microRNAs), which are associated with the occurrence and development of tumors, can directly or indirectly regulate autophagy. In particular, nuclear events induced by several epigenetic regulators can regulate the autophagic process and expression levels of tumor-associated genes, thereby promoting tumor progression. Tumor-associated microRNAs, including oncogenic and tumor-suppressive microRNAs, are of great significance to autophagy during tumor progression. Targeting autophagy with emerging epigenetic drugs is expected to be a promising therapeutic strategy for human tumors. From this perspective, we aim to summarize the role of epigenetic modification in the autophagic process and the underlying molecular mechanisms of tumorigenesis. Furthermore, the regulatory efficacy of epigenetic drugs on the autophagic process in tumors is also summarized. This perspective may provide a theoretical basis for the combined treatment of epigenetic drugs/autophagy mediators in tumors.