In order to explore the failure rule and protection technology of masonry walls under the combined effects of blast and fragment loading, the finite element program ANSYS/LS-DYNA was used to establish the model of masonry walls, fragments and explosives. The effects of the scaled distance, fragments size and initiation points on the displacement response of masonry walls were obtained. Both the ultimate load produced by explosive that the masonry walls can resist and the economical protective method of masonry walls under the protection of polyurea elastomer and steel mesh were obtained. The results show that the research method was reliable according to the comparison between the test results and simulation results. The scaled distance cannot be used to judge the damage severity of masonry walls under the blast and fragments loading. Decreasing the size of fragments can increase the damage of masonry walls in the same condition of fragments quality. The effect of different initiation points on the damage level of masonry walls was weak. The protection of polyurea elastomer and steel mesh can improve the blast resistance of masonry walls. When the distance from explosion was 1.2 m, the masonry wall protected by 5 mm polyurea elastomer and steel mesh can carry the load produced by the quality of equivalent TNT explosive between 8.296 kg and 11.376 kg. When the distance from explosion was 1.2 m and the equivalent TNT explosive quality was 2.4568 kg, 3 mm polyurea elastomer and steel mesh were the economical protective measure. The results can provide references for masonry walls anti-explosion theory and protection technology.