•Multi-negative stiffness amplification systems (NSAS) with improved damping effect.•Multi-location NSAS approach developed for complex underground structures.•Dual isolation of a column with a pair of NSASs for multi-intensity excitations.•Structural plastic energy dissipation burden significantly relieved by NSAS.•Residual deformation of columns avoided by the isolating ability of NSASs. Underground structures are vulnerable to strong earthquakes, with their central columns being prone to damage owing to their insufficient resistance capacity. In this study, an effective, hybrid, and multi-location seismic isolation approach was proposed for multi-floor and multi-span underground structures using several negative-stiffness amplification system-based isolation systems (NSAS-ISs). The NSAS-IS originated from the incorporation of an NSAS and an isolation bearing, which was proposed as a flexible connection installed at either the top or bottom of the central columns. The mechanical model as well as physical realization of the NSAS-IS was explored, and an improved damping mechanism was introduced. Subsequently, a multi-location isolation method was proposed with the NSAS-ISs installed at the top or bottom of the columns (corresponding to the 1-end-based isolation method) and at both the top and bottom of the columns (corresponding to the 2-end-based isolation method). The effectiveness and robustness of the proposed NSAS-IS pertaining to the structural seismic response mitigation of typical underground structures under different isolation methods were investigated, focusing on the underground structures buried at different depths subject to various seismic excitations at multiple intensities. The obtained results indicated the effectiveness of both the 1-end- and 2-end-based isolation methods for NSAS-IS in improving the seismic performance of multi-floor and multi-span underground structures, with significant improvement being observed in the damping and isolation effects. In particular, the 2-end isolation method was found to be considerably effective in multi-performance control for multi-intensity excitations and is thus suggested for underground structures with limited space for installation and isolation layers. Consequently, the plastic energy-dissipation burden of the primary structures can be significantly relieved, and the residual deformation of the columns can be avoided owing to their excellent isolation ability.