Cancer management and/or treatment require a comprehensive understanding of the molecular and signaling pathways involved. Recently, much attention has been directed to these molecular and signaling pathways, and it has been suggested that a number of biomolecules/players involved in such pathways, such as PI3K/Akt, NF-kB, STAT, and Nrf2 contribute to the progression, invasion, proliferation, and metastasis of malignant cells. Synthetic anti-tumor agents and chemotherapeutic drugs have been a mainstay in cancer therapy and are widely used to suppress the progression and, hopefully, halt the proliferation of malignant cells. However, these agents have some undesirable side-effects and, therefore, naturally-occurring compounds with high potency and fewer side-effects are now of great interest. Osthole is a plant-derived chemical compound that can inhibit the proliferation of malignant cells and provide potent anti-cancer effects in various tissues. Therefore, in this review, we presented the main findings concerning the potential anti-tumor effects of osthole and its derivatives and described possible molecular mechanisms by which osthole may suppress malignant cell proliferation in different tissues.