Cancer is one of the major causes of mortality in the world. Each year approximately 13 million people suffer from cancer disease, and approximately 60 % of them die because of cancer. Besides most of the patients response harmful side effects of chemo-and radiotherapies. Therefore the establishment of new therapeutic strategies for the treatment of cancers will be required. A number of studies have shown that some HSP are induced in specific tumor cells. For example, increased levels of HSP105, HSP90, HSP70, HSP60, HSP27 have been detected in colon cancer, lung cancer, hepatocellular carcinoma, colorectal cancer, and gliomas, respectively. Elevated HSP levels in tumor cells are suggested to be responsible for increased chemotherapy resistance and poor prognosis. Suppression of HSP expressions in cancer cells is a new strategy for the treatment. It is well known that some plant extracts and their flavonoids significantly decrease HSP expression, and induce apoptosis of cancer cells. In addition, using of the HSP inhibitors in association with classical chemotherapy increases the sensitivity of cancer cells to the cytotoxic drugs. Therefore, some plants and their biologically active natural compounds have been investigated for their possible contribution to cancer therapy. The current chapter reviews the role of HSP in different cancer types and suppressing HSP with some natural products.