Polyphenols can inhibit the enzymatic browning in food, but their indistinct synergistic effect and conformational change have limited their applications. In this paper, the mixture of quercetin, cinnamic acid and ferulic acid (Group 11, KI = 0.239 mM) possessed a higher inhibition ability than quercetin (KI = 0.361 mM), which could promote the spontaneous binding process. The final Group 11-tyrosinase complex is more stable, and the hydrophobic effect is the major driving force during the binding process. Moreover, there is not a direct relationship between the destruction of secondary structures and catalytic activity of tyrosinase. The interaction between ferulic acid and tyrosinase could destroy the secondary structures of enzyme but it had little impact on the tyrosinase activity. Molecular docking suggested that three polyphenols from Group 11 have synergistic effect on tyrosinase. This study provides new perspectives about the development of tyrosinase inhibitors in food products.