Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine‐derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. In addition, the impact of TCM treatment on DNA methylation, histone modification, and the regulation of noncoding RNAs is discussed. Furthermore, we have highlighted studies of TCM therapy that modulate the tumor microenvironment and eliminate cancer stem cells. The information compiled in this review will serve as a solid foundation to formulate hypotheses for future studies on TCM‐based cancer therapy.