As non-structural members, the masonry-infilled (MI) walls are always ignored in the numerical and experimental study on the blast and collapse resistance of RC frame buildings, while the contribution of MI walls on preventing the large-scale collapse has been observed according to the past explosion incidents. This paper aims to propose and verify a numerical simulation approach considering the blast- and collapse-resistant effects of MI walls, and further evaluate the collapse resistance of MI RC frame buildings under blast loadings. Firstly, based on our previously validated hybrid finite element (FE) modelling approach for RC frame structures and Multi-material Arbitrary Lagrangian-Eulerian method for applying blast loadings, the simplified micro-model and compressive strut model of the MI wall were adopted to characterize its blast and collapse resistance in the near- and far-regions of building, respectively. Secondly, the out-of-plane explosion test and in-plane quasi-static collapse test were numerically reproduced to verify the applicability of adopted FE modelling approaches for MI walls. Furthermore, by establishing the hybrid FE models of prototype bare and MI RC frame buildings, the propagation of blast waves, damage modes as well as dynamic responses of RC frame buildings under two design-based threat of explosion at corner and side columns were derived and examined. Finally, the applicability of the anti-collapse design method specified by U.S. Department of Defense, i.e., alternate path method (APM), for RC frame buildings under external explosions was examined. It derives that, (i) the presence of MI walls can efficiently block the blast waves into the building structures, and relieve the upward arch of slabs and damage degree of interior columns; (ii) compared with the bare RC frame buildings, the MI walls provide sufficient alternate load paths to enhance the structural robustness and restore the gravity stability of MI RC frame buildings after the explosions; (iii) the APM is only applicable to evaluate the collapse resistance of MI RC frames under the external explosion of cargo van bomb (1814 kg of equivalent TNT) or even less charge weight.