Autophagy is an intracellular lysosome-dependent catabolic process that is indispensable for maintaining cellular homeostasis through the turnover and elimination of defective or redundant proteins and damaged or aged organelles. Recent studies suggest that autophagy may be closely associated with tumorigenesis and the response of tumor cells to chemotherapeutic drugs. This article reviews recent advances in understanding the molecular mechanisms underlying the regulation of autophagy and the role of autophagy in oncogenesis and anticancer therapy. It is paradoxical that autophagy acts as a mechanism for tumor suppression and contributes to the survival of tumors. In addition, whether autophagy in response to chemotherapies results in cell death or instead protects cancer cells from death is complicated, depending on the nature of the cancer and the drug.