The identification of anticancer active ingredients and their molecular targets in traditional Chinese medicine is a great challenge in modern pharmacology research. Evodiamine is one of the bioactive components isolated from the fruit of Wu-Zhu-Yu and displays significant pharmacological activities, especially anti-inflammatory, antimicrobial, regulate metabolic syndrome and neuroprotective activity. Evodiamine has attracted great interest recently for its potential anticancer activities, and has also been found to inhibit the proliferation of various cancer cells and arrest cell cycle and cell migration. In recent years, evodiamine has been found to have potential toxic effects, mainly manifested as hepatotoxicity and cardiotoxicity. However, the pharmacological and toxicological mechanism of evodiamine is not clear. In this review, we summarized the anticancer effects of evodiamine and its target molecules in vitro and in vivo, focusing on key molecules such as HIF-1α, NF-κB and STAT3, and proposed that epigenetic modifications (DNA methylation, histone acetylation and microRNA) mediate the regulation of key molecules, which are still being explored and excavate into clinical practice.