Heat shock proteins (HSPs) are a defined set of chaperones for maintaining proper functions of proteins. The HSP70 family, one of the most inducible families in response to stress, protects cells from stress-induced cell death. It has been documented that HSP70s are highly expressed in various types of cancer cells and make the cells resistant to adverse microenvironments, such as hypoxia and glucose starvation, which are common features in malignant progression. Over-expression of HSP70s is thus associated with tumor transformation and eventually results in a decrease of chemotherapy efficacy. Notably, the distribution of HSP70s is deregulated in cancer cells. It has been reported that HSP70s localize distinct organelles or are exported to humoral circulation during cancer development. Either surface or exported HSP70s play danger signals and trigger immune response to destroy the tumor cells. In this review, we lay out recent advances in the HSP70s-mediated cancer diagnosis and therapy. This review would be enlightening for clinical cancer medicine.