Cichorium intybus L. (Chicory) is a widely distributed, edible, perennial, herbaceous member of the Asteraceae family. Besides its use in modern Chinese herbal medicine, its ethnomedicinal use is evident in the text from ancient Greece, Egypt and China. It is also used as a food and coffee substitute, which is mainly responsible for its extensive domestication. In recent decades, cytotoxic studies of C. intybus extracts have shown its antitumor potential. These studies also identified metabolite constituents including guaianolides, 6‑methoxyflavone, eudesmanolides, germacranolides, polyacetylene, sterol, anthocyanin, delphinidin, 3,4‑dihydroxyphenethyl and other novel compounds. Many of these phytometabolites have shown positive cytotoxic activities in vitro, and antitumor action in vivo and in clinical trials, demonstrating the potential of C. intybus metabolites as antitumor drugs. Structural activity relationship studies have further confirmed these bioactivities. In this review, we focused on the phytochemicals of C. intybus with reported cytotoxicity and potential antitumor properties. We also discuss their specificity towards tumor cells, structural activity relationship, the involved signaling pathways and molecular mechanism, with the expectation of the future development of efficient and targeted antitumor therapeutic strategies.