Concrete-filled steel box columns have been widely used in medium- and high-rise buildings in Taiwan; however the research of these columns in fire is limited. This study aims to investigate the behavior of the concrete-filled steel square box columns exposed to fire. Ten large-scale specimens were constructed and tested under constant axial compression and exposed to standard fire. The test results indicate that the axial deformation history of the specimens was the axial expansion owing to increasing temperature, and contraction due to the strength deterioration of the materials until failure. The failure was caused by the strength deterioration owing to elevated temperatures. The failure mode involved outward bulges of the steel plate of the column and crushing of the concrete. The magnitude of the constant axial compression highly affected the axial deformation history and fire resistance, but the size of the cross-section and shear stud had little effect on the fire behaviors. Based on the test results, an empirical formula was proposed to predict the fire resistance of the concrete-filled steel square box columns that will benefit the performance-based fire resistance design.