Abstract: Under tensile, torsional and bending conditions, the superconducting tape may become defective, reducing its critical current. In this paper, the numerical simulation analysis of multi-layer high-temperature superconducting cable composed of yttrium barium copper oxide (YBCO) coated conductors was carried out in the case of defects. Different models of defective tapes with different distributions in the same and different conductor layers were built. From these models, the effects of different distributions of defective tapes on the critical current and in turn, the AC loss in multi-layer HTS cables were analyzed. It is found that, in the case of defective tapes in the same conductor layer, the AC loss depends on the quantity and degree of defect, whereas it is independent of defect distribution. In the case of defects in different conductor layers in multi-layer HTS cable, a higher loss is observed when most defects are located near the outermost layer, whereas a smaller loss is observed when most defects are present near the middle layer. When 8 defective tapes are present in 56 tapes, the maximum AC loss is observed in C3 and C4 conductor layers with a critical current degradation rate of 40%, which is 18.80% higher than that of non-defective tapes. In order to avoid the additional AC loss caused by defects, it is necessary to consider retaining a certain margin of the cooling system in actual operation. The work provides a theoretical basis and application reference for the study of AC loss of multi-layer HTS cable with defective tapes.