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This Letter addresses a new finding of the connection between the macroscopic fatigue cracking behaviors of twin boundaries (TBs) and the microscopic TB-dislocation interactions. According to the difference in crystallography beside TBs, slipping dislocations usually interact with TBs in different modes during plastic deformation. In this study, fatigue cracking behaviors at the TBs in Cu and Cu alloys were investigated and compared theoretically and experimentally based on these different interaction modes. The results reveal that the TB-dislocation interactions strongly affect the interfacial strength of TBs through influencing the damage degree by the penetrated dislocations during low-cycle fatigue tests.