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Mortality‐to‐incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether‐à‐go‐go‐1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration‐dependent manner (IC50 of 69.97 ± 5.2 μM), and the amino acids Ile 550, Thr 552, and Gln 557 in the Eag1 C‐linker domain were critical for tetrandrine's inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentration‐dependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell‐transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction‐induced diseases. We identified the first natural inhibitor of ether‐à‐go‐go‐1 (Eag1), the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction‐induced diseases. [ABSTRACT FROM AUTHOR]