This study aimed to evaluate the inhibition properties of 50% ethanol extract from Solanum lyratum Thunb. (SLEE) toward the activity of tyrosinase. When using L-3,4-dihydroxyphenylalanine (L-dopa) as the substrate for mushroom tyrosinase, SLEE showed inhibitory effect on the activity of mushroom tyrosinase. SLEE decreased the value of Vmax and increased Km, and it behaved as a mixed-type inhibitor toward mushroom tyrosinase. Human malignant melanoma A375.S2 cell line was also used to evaluate the influence of SLEE on tyrosinase activity in the cell. It was found that SLEE reduced the tyrosinase activity in the A375.S2 cells at medium and high enzyme substrate levels (L-dopa, 0.5 and 1.0 mg/ml, respectively), but not at low enzyme substrate level (0.1 mg/ml). It was concluded that SLEE might be a potential inhibitor of tyrosinase.