The influence mechanism of crack orientation on B2 phase crack propagation behavior under cyclic loading is studied by using the meta-atom molecular dynamics (MAMD) method, and the simulation results are compared and verified based on the theory of linear elastic fracture mechanics. According to the different propagation speed of crack in B2 phase matrix, the crack propagation process can be divided into three stages: elastic stage, rapid propagation stage and slow propagation stage. The toughness or brittleness of the crack mainly depends on the competition between the cleavage fracture of the atomic bond and the plastic slip at the crack tip. The crack propagation behavior is obviously orientation dependent. Orientation I and orientation II expand in the form of ductile fracture. Orientation III shows obvious brittleness and expands in the form of cleavage fracture. Orientation IV (Orientation I-IV represent the four angles between the crack plane and the crystal orientation) shows both ductile fracture and brittle cleavage fracture. The defects and stress concentration at the crack tip provide a driving force for martensitic nucleation, and the hcp phase produced by martensitic transformation effectively increases the toughness of the crack. The simulation results of molecular dynamics are basically consistent with the theoretical prediction of linear elastic fracture mechanics. This suggests that the variation of the orientation could tune the crack tip plasticity and toughening in B2 phase matrix.