Zeolite 4A, synthetic silicate, has been shown to exhibit diverse biological activities such as anti-cancer and anti-oxidant activity. In the present study, we report that the zeolite 4A may improve skin-whitening. We found that zeolite 4A inhibited melanin production in a dose-dependent manner, which has not cytotoxicity. Zeolite 4A also inhibited alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin synthesis in B16F10 cells. Interestingly, zeolite 4A decreased alpha-MSH-induced tyrosinase activity in B16F10 cells, which did not inhibit tyrosinase activity under cell-free conditions. The results of this study indicate that zeolite 4A may reduce pigmentation by way of an indirect nonenzymatic mechanism. We also found that zeolite 4A decreased alpha-MSH-induced microphthalmia-associated transcription factor (MITF) and tyrosinase expression and that zeolite 4A induced the activation of extracellular signal-regulated kinase (ERK). These results suggest that the depigmenting effect of zeolite 4A may result from the down-regulation of MITF and tyrosinase expression by increasing ERK activity. The results thus provide evidence that zeolite 4A can be used as a potential skin-whitening agent.