The problem of cracking and long-term deflection in larger-span prestressed concrete box girder bridges exists throughout the world and has restricted the development of long-span concrete bridges to some extent. However, the understanding of cracking and deflection of concrete box girder bridges is still insufficient and many strengthening methods cannot reach anticipated effect. In this paper, a space-frame lattice model which is used to analyze the stress on the entire cross-section of the box girder bridge, is presented. The stress state of random grid elements in the model may be biaxial in plane. The model simulates the cracking and deflection of pre-stressed concrete box girder bridges. This model was applied for cracking and deflection analysis of the existing concrete box girder bridge with (80+100+80) m spans. The calculation results are compared with the actual status of the bridge. The paper indicates that cracking of girder becomes one of major factors which have influence on deflections of long span prestressed concrete bridges. The space-frame lattice model is an effective tool to analyze the cracking and deflection of prestressed concrete box girder bridges and merits further investigation.