Aiming at the problem of floor cracking in the closing process of prestressed concrete box girder in cantilever construction, the failure mechanism and prevention are studied in this paper. Taking a prestressed concrete continuous box girder bridge as an example, the construction process of the box girder is simulated, the cracking process of the bottom plate is simulated by considering the material nonlinearity, and the mechanism of the bottom plate cracking is analyzed. On this basis, the prevention and control measures are proposed for design and application according to the code. The results show that the hole rib is the most disadvantageous area due to the influence of the closing beam, and the inclined crack and tearing crack of the hole rib are the main causes of the failure of the box girder under the action of radial force. In the future design of box girder, the transverse base plate should meet the shear bearing capacity, and the hole ribs should meet the requirements of minimum hole spacing.