In recent decades, terrorist attacks and accidental explosions have occurred frequently. The casualties are not only caused by the shock wave, but also by the structural collapse initialed from the failure of structural columns. In this paper, the dynamic response and damage mechanism of prefabricated reinforced concrete (RC) columns with steel joints (PRC) subjected to blast loads are numerically investigated. By comparing the numerical results with the experimental results, the accuracy of the finite element (FE) model is firstly verified. Then, dynamic responses and damage of PRC under blast loads induced by the TNT explosions and vapor cloud explosions (VCEs) are investigated and compared with each other. The results indicated that PRC damage under VCEs with 9.3 MPa is larger than that under TNT explosions. Conversely, the damage under VCEs with 7 MPa is smaller than that under TNT explosions, and the blast-induced damage and dynamic behavior of PRC under two types of explosions is different. Subsequently, parametric studies are further carried out to investigate the influence of key parameters of PRC, including longitudinal and transverse reinforcement ratio, column dimensions, concrete strength, steel sleeve dimensions on PRC damage. It is revealed that different parameters affect the damage for PRC column in different load regions of P-I diagrams, including the impulsive load region, dynamic load region and quasi-static load region. Increasing the sleeve length, sleeve ratio and transverse reinforcement ratio improves the shear-resistant performance of PRC, and these parameters more easily affected PRC damage in the impulsive load region. Increasing the concrete strength and column depth can increase the blast-resistant performance of PRC in three load regions. Based on parametric studies, pressure-impulse (P-I) diagrams for damage evaluation of PRC under VCEs and TNT explosions are proposed and verified. Finally, Blast-resistant design procedure of PRC based on P-I diagram is developed.