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Background: Ligularia fischeri is a perennial herb isolated from plants of the Asteraceae family. Ligularia fischeri is distributed throughout Korea, Japan, eastern Siberia, and China. Aims: The aim of this study is to examine the intracellular inhibitory effect of Ligularia fischeri ethanol extract on melanin synthesis and expression of tyrosinase and tyrosinase‐related protein 1 and 2. In addition, we analyzed the mitogen‐activated protein kinase signaling pathway and microphthalmia‐associated transcription factor in alpha‐melanocyte‐stimulating hormone‐stimulated B16F10 melanoma cells. Methods: To assess the inhibition of melanogenesis in alpha‐melanocyte‐stimulating hormone‐stimulated B16F10 melanoma cells, the expression of melanogenesis‐related genes was investigated by quantitative real‐time polymerase chain reaction, while western blotting was performed to determine protein expression levels. Results: We confirmed that the ethanol extract of Ligularia fischeri inhibited melanin synthesis in vitro by decreasing tyrosinase and tyrosinase‐related protein 1 and 2 expression. Furthermore, we revealed that tyrosinase expression was regulated by the suppression of microphthalmia‐associated transcription factor expression and activation of extracellular signal‐regulated kinase phosphorylation. The ethanol extract of Ligularia fischeri inhibited melanogenesis by activating extracellular signal‐regulated kinase phosphorylation and suppressing microphthalmia‐associated transcription factor and tyrosinase expression. Conclusions: Ligularia fischeri ethanol extract may be used as an effective skin whitening agent in functional cosmetics. [ABSTRACT FROM AUTHOR]