Melanin is synthesized by tyrosinase to protect the skin from ultraviolet light. However, overproduction and accumulation of melanin can result in hyperpigmentation and skin melanoma. Tyrosinase inhibitors are commonly used in the treatment of hyperpigmenta-tion. Natural tyrosinase inhibitors are often favoured over synthetic ones due to the poten-tial side effects of the latter, which can include skin irritation, allergies, and other adverse reactions. Nuciferine, an alkaloid derived from Nelumbo nucifera , exhibits potent antioxi-dant and anti-proliferative properties. This study focused on the in silico screening of nu-ciferine for anti-tyrosinase activity, using kojic acid, ascorbic acid, and resorcinol as stan-dards. The tyrosinase protein target was selected through homology modeling. The residues of the substrate binding pocket and active site pockets were identified for the purposes of grid box optimization and docking. Therefore, nuciferine is a potent natural tyrosinase in-hibitor and shows promising potential for application in the treatment of hyperpigmenta-tion and skin melanoma.