The purpose of this study was to demonstrate the effects of KHG26792, a potential new skin-whitening agent and to identify the mechanisms of the action. KHG26792 significantly reduced melanogenesis via activation of extracellular signal-regulated kinase (ERK) in a dose- and time-dependent manner. Also, microphthalmia-associated transcription factor (MITF) was downregulated through phosphorylation of ERK, but tyrosinase, the rate-limiting enzyme was not inhibited directly. Moreover, we showed the hypopigmentary effects of KHG26792 in the pigmented skin equivalents established with Cervi cornus Colla (deer antler glue). It was found that the color of pigmented artificial skin became lightly after treatment of KHG26792. Our findings suggest that KHG26792 is a novel candidate compound for a skin whitening agent.