In this work,we studied the synthesis,cytotoxicity assay,and molecular docking of hydroxychalcone derivatives as tyrosinase inhibitors.Synthesis of chalcone derivatives was carded out through a Claisen-Schmidt condensation reaction between acetophenone and benzaldehyde derivatives under alkaline conditions for 48 h.The synthesized products were characterized by using Fourier transform infrared (FTIR),gas chromatography-mass spectrometry (GC-MS),proton and carbon nuclear magnetic resonance (1H and 13C NMR) spectrometer.The in vitro inhibitory activity was evaluated against tyrosinase enzyme by employing L-3,4-dihydroxyphenylalanine (L-DOPA) as the substrate.We successfully synthesized 4-hydroxychalcone (HC) and 4-hydroxy-3-methoxychalcone (HMC) with a yield of 60％ and 76％,respectively.While the tyrosinase inhibitory test of HC and HMC gave the IC50 value of 64.35 and 21.56 μg/mL,respectively,demonstrating that their inhibitory activities against tyrosinase enzyme were better compared with kojic acid and hydroquinone as the positive controls.We also found that HC gave 2025 μg/mL as the IC50 value against Vero cells,confirming that it was not toxic to the normal cell line.The molecular docking study gave the root-mean-square deviation value of less than 2(A).Furthermore,the binding energies of hydroxychalcone derivatives were found as-30.13 and-31.38 kJ/mol,showing that those compounds could be potentially used as the alternative tyrosinase inhibitors in medical application.