Thirteen kojic acid-coumarin derivatives were synthesized using the principle of molecular hybridization, and their structures were characterized by H NMR, C NMR, and HRMS. enzyme inhibition experiments showed that all newly synthesized derivatives have excellent inhibition of tyrosinase (TYR) activity. As a mixed inhibitor, compound has the strongest activity, with an IC value of 0.88 ± 0.10 µM. Multispectral experiments have confirmed that the mode of action of compound on TYR was static quenching. In addition, compound formed a new complex with TYR, which increased the hydrophobicity of the enzyme microenvironment, reduced the content of the α-helix in the enzyme, and changed the secondary structure. The experimental results showed that compound effectively inhibited the browning of lotus root slices and had low cytotoxicity. Therefore, compound is believed to have great development potential as a TYR inhibitor in the food industry.