Cashew nut shell liquid (CNSL); extracted from cashew nut shell, is an abundant natural resource. Cardanols were the major phenolic components isolated from CNSL. In this research, we reported on the inhibitory mechanism of cardanols on tyrosinase for the first time. We studied the functions of cardanols and revealed the underlying mechanism of cardanols as tyrosinase inhibitors. Cardanol triene, cardanol diene and cardanol monoene could decrease the steady-state rate of the tyrosinase diphenolase activity efficiently. The IC50 values of three cardanol compounds were determined to be 40.5 +/- 3.7, 52.5 +/- 3.2 and 56.0 +/- 3.6 mu M (n =3), respectively. Meanwhile, the kinetic analysis and the intrinsic/ANS-binding fluoresecence-quenching showed that one cardanol might enter into one tyrosinase. The characteristic values further revealed that cardanols could interact with tyrosinase. Besides, computational study with molecular docking implied that cardanols might affect the amino acid residues of the tyrosinase active site. Collectively, cardanols could moderate inhibitory activities on tyrosinase effectively. (C) 2016 Published by Elsevier Ltd.