An advanced large-scale sodium-cooled fast reactor named JSFR adopts an innovative two-loop cooling system. This cooling system design raises major technological issues: hydraulic and structural integrity due to the increase in one-loop coolant flow rate, safety design against the break or failure in one-loop piping, and ensuring the reliability of the decay heat removal system (DHRS). The present paper describes the investigation of the piping structural integrity due to flow-induced vibration using a 1/3-scale hot-leg piping test. The structural integrity of the hot-leg piping in the JSFR design has been confirmed by a flow-induced vibration analytical methodology, verified with the experimental data. Additional experimental results have revealed that hydraulic issues including gas entrainment and vortex cavitation could be prevented by some design measures. By applying appropriate safety design, the two-loop system has been confirmed to be valid against the break or failure in one-loop piping by a safety evaluation in this study. The DHRS with natural circulation is designed in conformity with the two-loop system by introducing adequate safety designs. In this paper, the validity of this DHRS is given by a probabilistic safety assessment and safety evaluation.