<p>Heat shock proteins (HSPs) play an important role in several tumors; contribute to anti-cancer drug resistance, cell proliferation, and metastasis; and have been suggested as a major cause of failed anti-cancer drug treatment. In addition, cancer stem cells (CSCs) have been identified in many types of malignancies, including leukemia, breast, colorectal, and brain cancers, and are a leading cause of failed cancer treatment owing to their anti-cancer drug and radiation therapy resistance. Therefore, many researchers, including our group, have investigated and developed natural products that target chemotherapy resistance factors in cancer cells. This review introduces the inhibitors of chemotherapy resistance factors discovered using a unique assay system.</p> Graphical Abstract <p></p>