Autophagy is a major self-degradative intracellular process required for the maintenance of homeostasis and promotion of survival in response to starvation. It plays critical roles in a large variety of physiological and pathological processes. On the other hand, aberrant regulation of autophagy can lead to various cancers and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Crohn's disease. Emerging evidence strongly supports that epigenetic signatures, related non-coding RNA profiles, and their cross-talking are significantly associated with the control of autophagic responses. Therefore, it may be helpful and promising to manage autophagic processes by finding valuable markers and therapeutic approaches. Although there is a great deal of information on the components of autophagy in the cytoplasm, the molecular basis of the epigenetic regulation of autophagy has not been completely elucidated. In this review, we highlight recent research on epigenetic changes through the expression of autophagy-related genes (ATGs), which regulate autophagy, DNA methylation, histone modifications as well as non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and their relationship with human diseases, that play key roles in causing autophagy-related diseases.