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Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood. To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT. SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting. SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and β-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors. In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/β-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma. Image 1 • An ethanolic extract of Si-Jun-Zi-Tang , a traditional Chinese medicine formula, suppresses B16 melanoma growth in mice. • Si-Jun-Zi-Tang regulates the miR-34b/c-Met/β-catenin pathway in B16 tumors. • This study provides pharmacological justifications for the traditional use of Si-Jun-Zi-Tang in treating melanoma. [ABSTRACT FROM AUTHOR]