Autophagy is an evolutionarily conserved machinery for intracellular homeostasis via lysosomal degradation system in practically all cells in humans. Defective autophagy can cause a wide variety of diseases, particularly cancer. Autophagy not only provides a tumor-suppressive role in early stage, but it also assists as a tumor supporter in cancer malignant stage. Thus, multiple lines of evidence from human genetic and molecular works have decorated the importance of the autophagy machinery in cancer biology. Abnormal autophagy governs healthy normal cells to endure transformation of malignant cells. By comparison, cancer cells are apt to control autophagy to bloom, in spite of detrimental tumor microenvironment, and to repel therapeutic challenges. Hence, modulation of acidification in autophagic flux has been expected as a new approach to assassinate malignant cells or sharpen them to therapy. Most current research is trying to manipulate autophagy appropriately for cancer therapies, and a wide variety of medical objectives are turning forward to inhibit acidification of autophagic flux with repurposing drugs. This chapter discusses how repurposing drugs like current chloroquine analogues can be used to treat cancers in preclinical and clinical studies.