In order to study the potential mechanism of unexpected ignition of confined charge in the process of penetrating multi-layer target, by integrating the designs of multi-layer nested strikers and bidirectional limited structure, a nonlinear amplification experimental method of confined charges under continuous multiple impacts loading was established. The effectiveness of the experimental method, and the intrinsic mechanism of nonlinear response amplification were analyzed. The influence of nonlinear response of charges under multiple impacts loading on ignition behaviors was studied. The results show that the experimental method can implement multiple impacts loading with sub-millisecond pulse width, and 100 MPa-scale peak stress value. When the characterized frequency of loading is close to the intrinsic frequency of confined charges, structural nonlinear response amplification emerges, and the stress amplitude increases gradually. For the same striker velocity and mass, while varying frequency of loading, the PBX-3 charges could be ignited if structural nonlinear response is amplified and could not be ignited if structural nonlinear response is not amplified. It is found that the structural nonlinear response amplification effect is an important factor leading to charge ignition.