This study explores the effect of harmine, a natural compound, on melanin synthesis through its interaction with the tyrosine kinase signaling pathway. It is hypothesized that harmine, by inhibiting this pathway, may activate pigment degradation and tested by evaluating how harmine affects the key molecules in the tyrosine kinase pathway. The experiments are carried out using GES-1 and B-16 cells as samples. The MTT assay is used to evaluate cell viability. The ELISA assay is used to quantify the melanin content. It is found that the cell viability of B-16 cells still maintains at a high level under the 25 μM harmine treatment within 96 hours. Additionally, the melanin content in B-16 cell superannuate decreases with the increasing of harmine concentration within 96 hours. This work could provide insights into new depigmentation therapies by targeting tyrosine kinase regulation.