Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. Recently, numerous biological activities such as cytotoxic effect on leukemia cells, and antitumor, neuroprotection, and antibacterial activities have been reported for this compound. Although a number of proteins including protein kinase C, androgen receptor, and acetylcholinesterase were proposed as molecular targets responsible for the activities of decursinol, they are not enough to explain such a diverse biological activity mentioned above. In this study, we employed a chemical proteomic approach, leading to identification of seven proteins as potential proteins interacting with decursinol. Most of the proteins contain a defined ATP or nucleic acid binding domain and have been implied to be involved in the pathogenesis and progression of various human diseases including cancer, autoimmune disorders, or neurodegenerative diseases. The present results may provide clues to understand the molecular mechanism of the biological activities shown by decursinol, an anticancer natural product.