In this paper, the influence of the number of isolated main heat exchangers (MHXs) on the integral pressurized water reactor (IPWR) is studied with the RELAP5 code. The primary loop of integral pressurized water reactors (IPWRs) is integrated layout within the reactor pressure vessel (RPV), and several MHX cassettes are located between the core support and the pressure vessel. Since the MHX has a closed tube tank, it is difficult to plug the heat exchanger tubes. In case of heat exchanger tube damage, it is necessary to isolate the main heat exchanger cassette. The consequences of isolating the MHX are the reduction of total heat transfer surface, the decrease of the flow area, and subsequent reduction of the primary system natural circulation flow, which leads to the reduction of reactor power and economic efficiency. The purpose of this paper is to analyze whether MHX isolation has an impact on reactor operation. First, the steady state operational characteristics with different numbers of isolated MHX of the nuclear heating reactor (one kind of IPWR) are studied with RELAP5 code. The results of the analysis show that isolating 2 MHXs is around the limit for reactor normal operation. Moreover, the transient thermal–hydraulic characteristics of station blackout (SBO) event have been analyzed to find out whether the isolating of MHX could affect the long-term cooling capacity. The results show no significant impact on the SBO event.