In traditional Chinese medicine (TCM) theory, pathogenic heat and toxins, which are akin to the inflammatory factors, are the causes of cancer and could promote its virulent development. Therefore, heat-clearing and detoxicating (HCD) herbs are essential components of TCM formulas for cancer treatment. An increasing interest has been focused on the study of HCD herbs and accumulated evidences have shown that HCD herbs or HCD herbs-based formulas exhibited remarkable anticancer effects when used alone or combined with other therapeutic approaches. Some of the HCD herb-derived products have been tested in clinical trials. Studies revealed that extracts or pure compounds of the HCD herbs showed a broad anticancer spectrum against both solid and hematologic malignancies without significant toxic effects. Notably, some HCD herbs or formulas could strongly enhance the anticancer activities of chemo-or radio-therapy and alleviate their side effects. The anticancer activities of HCD herb exacts or the pure compounds were reported to be through multiple cellular or molecular mechanisms, such as induction of cancer cell apoptosis, differentiation and cell cycle arrest, inhibition of cancer cell growth, invasion and metastasis, and inhibition of tumor angiogenesis. In this review, we provide comprehensive analysis and summary of research progress and future prospects in this field to facilitate the further study and application of HCD herbs.