<p>Cancer is one of the most important causes of mortality worldwide, and its incidence is increasing annually in both developed and developing countries. Up to now, chemotherapy has been a commonly used treatment for cancer. However, due to its significant side effects, other complementary or alternative treatments are needed as adjunctive therapies. The active chemical components extracted from herbal medicine are characterized by lower toxicity and fewer side effects compared to traditional anti-cancer drugs. Recently, the anti-tumor effects of saffron (<i>Crocus sativus</i> L.) and its bioactive components crocins, crocetin, safranal, and picrocrocin (isolated from the stigma of saffron) have been extensively explored. The biological activities of saffron include the inhibition of DNA, RNA, and protein synthesis, induction of cytotoxic effects, inhibition of inflammatory responses, epigenetic regulation, etc. Thus, this review aims to provide an overview of the anti-cancer properties and epigenetic effects of saffron, as well as theoretical foundations for its bioactive components as effective synergistic agents for cancer therapy.</p>