In order to investigate the effects of tea polyphenols on the conformation and antigenicity of α_s1-casein, epigallocatechin gallate (EGCG) and epigallocatechin (EGC), tea polyphenols with high bioactivity, were used for grafting onto α_s1-casein. The conformational changes of α_s1-casein were studied by fluorescence, synchronous fluorescence and circular dichroism (CD) spectroscopy, and the changes in the antigenicity of α_s1-casein were analyzed by indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and Western blot assay. The results showed that EGC and EGCG both quenched the fluorescence of α_s1-casein, and affected the Tyr and Trp residues of α_s1-casein. The α-helix and β-sheet contents of α_s1-casein increased slightly, and the random coil content decreased slightly. The conformational change of α_s1-casein resulted in a significant decrease in the antigenicity of α_s1-casein. The effect of EGCG on the conformation and antigenicity of α_s1-casein was stronger than that of EGC.