<p><i>Stephania tetrandra</i> S. Moore (<i>S. tetrandra</i>) is an essential traditional Chinese medicine used to treat arthralgia from rheumatism, wet beriberi, dysuria, eczema, and inflamed sores. <i>S. tetrandra</i> contains numerous active components and demonstrates diverse pharmacological properties. Notably, its potent anticancer activity has increasingly been the focus of attention. Despite this, comprehensive reviews on the anticancer effects of <i>S. tetrandra</i> are scarce. Recent research has shown that <i>S. tetrandra</i> alkaloids exhibit anticancer properties through several molecular mechanisms, including apoptosis induction, autophagy induction, inhibition of invasion and metastasis, cell cycle arrest, reversal of multidrug resistance, and enhancement of radiation sensitization in cancer cells. This review provides a detailed summary of the research developments and challenges associated with the anticancer activities of <i>S. tetrandra</i> in cancer. It specifically explores the underlying molecular mechanisms of its anticancer effects, both in vitro and in vivo. Additionally, this review investigates the structural modification of active alkaloids in <i>S. tetrandra</i> to improve its anticancer efficacy and offers suggestions for further research. Therefore, this review aims to offer robust theoretical support for further clinical research and the development of anticancer agents based on <i>S. tetrandra</i>.</p>