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Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.

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