The interaction between metals is ubiquitous, but there is still a lack of quantitative models considering the interaction between metals, which leads to the deviations in predicting the joint toxicity of metals. The present study estimated the uptake rate constants (kin) and elimination rate constants (kout) and elucidated how the presence of one metal (Cu or Cd) affects the absorption and excretion of another metal (Cd or Cu) in zebrafish larvae. The results showed that Cd and Cu inhibited each other in the process of absorption and excretion by comparing separately kin and kout of Cd or Cu with the other metal Cu or Cd mixed concentrations increased, thereby affecting the Cd and Cu bioaccumulation in the zebrafish larvae. Then the interactions between Cd and Cu in the uptake and elimination processes were quantified to obtain a refined toxicokinetic model. Verification with independent experiment data showed that the refined toxicokinetic model could significantly improve the prediction of the Cd or Cu bioaccumulation in the zebrafish larvae. This study contributes to understand the toxicokinetic process of the Cd-Cu mixture in the zebrafish larvae, and the developed model could be used to predict the toxicity of the metal mixtures. •Cd and Cu inhibited each other in the process of absorption and excretion.•A refined toxicokinetic model considered the interaction was developed.•The refined toxicokinetic model can accurately predict the accumulation of Cd-Cu.