In order to analyze the effect of fastener stiffness and damping on the box-girder noise, a mixed FEM-BEM noise prediction model based on train-track-bridge coupling vibration theory and acoustical BEM theory was built and validated by field test. A 32 m simply-supported box-girder was selected as the case study, the effects of fastener stiffness and damping on the distribution of noise field, characteristics of noise spectra and wheel/rail interaction force were investigated. Results show that the mixed FEM-BEM model is a good predictor, the dominant frequency range of structure-borne noise is 40～80 Hz which mainly depends on the fastener stiffness; the sound pressure levels (SPLs) of the field points with a height of 1.2 m from the ground have an attenuation rate of 0.29 dB(Lin)/m and 0.067 dB(Lin)/m respectively in the distance of 10～40 m and 40～100 m from the nearest track centerline; the direction angle of structure-borne noise decreases significantly with the increase of the fastener stiffness; when the fastener stiffness varies from 10 MN/m to 100 MN/m, the average SPLs increase 12.5 dB(Lin) for the field points in the longitudinal section that has a distance of 30 m from the nearest track centerline, and the peak frequencies of structure-borne noise and wheel/rail interaction force vary from 30 Hz to 67 Hz simultaneously; the fastener damping has little effect on the directivity of the noise field; when the fastener damping ratio varies from 0.0625 to 0.5, the average SPLs decrease 5.0 dB(Lin) for the field points in the longitudinal section that has a distance of 30 m from the nearest track centerline, and the peak frequencies of the structure-borne noise and wheel/rail interaction force remain unchanged.