In this study, the interaction mechanism of bovine serum albumin (BSA) with tannic acid (TA) was investigated by spectroscopic and computational approaches and further validated using circular dichroism (CD), differential scanning calorimetry (DSC) and molecular docking techniques. The fluorescence spectra showed that TA bound to BSA and underwent static quenching at a single binding site, which was consistent with the molecular docking results. And the fluorescence quenching of BSA by TA was dose-dependent. Thermodynamic analysis indicated that hydrophobic forces dominated the interaction of BSA with TA. The results of circular dichroism showed that the secondary structure of BSA was slightly changed after coupling with TA. Differential scanning calorimetry showed that the interaction between BSA and TA improved the stability of the BSA-TA complex, and the melting temperature increased to 86.67 °C and the enthalpy increased to 264.1 J g-1 when the ratio of TA to BSA was 1.2 : 1. Molecular docking techniques revealed specific amino acid binding sites for the BSA-TA complex with a docking energy of -12.9 kcal mol-1, which means the TA is non-covalently bound to the BSA active site.