Autophagy is a catabolic process that targets impaired organelles and proteins for lysosomal degradation to maintain cell hemostasis. Autophagy in cancer is dynamic and, more specifically, depending on the stage and type of tumor. Researches in genetically engineered mouse models are agreed with the concept that autophagy can constrain initiation of the tumor by controlling oxidative stress and DNA damage, while in established tumors, autophagy can also be required for tumor survival. As shown in preclinical models, suppression of autophagy restored chemotherapy sensitivity against tumor cells. Targeting autophagy in cancer will develop a new era for anti-cancer drugs, but more specific and potent inhibitors of autophagy are needed. The role of autophagy in cancer cells continues to emerge, and further studying to identify optimum strategies to modulate autophagy for therapeutic advantage