Abstract: Provided are an antibody that binds to Staphylococcus aureus alpha-hemolysin or a fragment thereof, and the use of the antibody or the fragment thereof for preventing or treating Staphylococcus aureus infections. The antibody is obtained through screening by means of the strategies of attenuated immunity and virulent screening of alpha-hemolysin, and the antibody has high affinity to alpha-hemolysin, can effectively block the hemolysis effect of alpha-hemolysin, has proved significant protective or therapeutic effects in the alpha-hemolysin sepsis model, MRSA bacteremia model and MRSA lung infection model, and has a synergistic effect with antibiotics, which is a beneficial supplement to existing antibiotic therapy for Staphylococcus aureus.