Abstract: Effect of high hydrostatic pressure treatment on the antigenicity and structure of β-conglycinin was studied to provide a method for the desensitization of soybean protein. In this study, β-conglycinin was extracted by using isoelectric point precipitation method and then processed under different high hydrostatic pressure conditions. The immunological activity of β-conglycinin was determined by Western-Blot and ELISA. SDS-PAGE, Fourier transform infrared spectroscopy and fluorescence spectroscopy were used to characterize the structure of β-conglycinin. The results showed that high hydrostatic pressure treatment significantly changed the antigenicity and structure of β-conglycinin. Under the pressure of 400 MPa, the immunological activity of β-conglycinin was minimized with significant change in the secondary and tertiary structures of protein. Contents of α-helix and β-turn were reduced, while contents of β-sheet and random coils were increased obviously, causing a large number of hydrophobic regions to be exposed. These results provide evidence that high hydrostatic pressure treatment changes the spatial structure of β-conglycinin, which may destroy or mask the original antigenic epitope, thereby lowering the antigenicity of β-conglycinin.