We investigated the in vitro effects of p-coumaric acid on melanogenesis. The melanin content in B16F1 cells stimulated with p-coumaric acid significantly decreased (68 % vs. control) through inhibition of tyrosinase enzyme activity assessed using both cell-free and cell-based assays (46 and 27 % compared with control, respectively). In addition, stimulating B16F1 cells with p-coumaric acid reduced cyclic adenosine monophosphate (cAMP)—responsive element-binding protein (CREB) protein phosphorylation (26 % vs. control), which in turn downregulated the expression of the microphthalmia-associated transcription factor (MITF) and its target gene tyrosinase (27 and 20 % vs. control, respectively). p-Coumaric acid has a hypopigmentation effect in melanocytes by both directly inhibiting tyrosinase enzyme activity and reducing CREB phosphorylation, which inhibits MITF and tyrosinase expression.