The triple natural circulation is adopted for the design of the passive residual heat removal (PRHR) system of the integrated small reactor. After the large break of intermediate loop pipeline, the secondary side of the main heat exchanger will be emptied. Whether the triple natural circulation can be reestablished and the core decay heat can be continuously taken away is very important for reactor safety. In this paper, an overall analytical model including the core, primary loop, intermediate loop and PRHR was established based on RELAP5 code to analyze the large break of intermediate loop accident for the integrated small reactor, and the influence of different nozzle positions of PRHR makeup tank was studied. The analysis results show that after the large break of intermediate loop, the PRHR makeup tank can replenish water to the PRHR timely and finally establishes a stable single-phase natural circulation to remove the core decay heat, and then takes the reactor to the safe state; PRHR makeup tank nozzle located at the inlet of air cooler will lead to reverse natural circulation flow under accident, which is not conducive to long-term cooling of reactor. It is suggested that the nozzle of the makeup tank should be set at the pipeline between the isolation valve and the air cooler outlet to ensure the positive single-phase natural circulation flow and improve the safety of the reactor.