Abstract: The main steam line break (MSLB) accident of ACP600 advanced third generation nuclear power plant is taken as the research object. The MSLB accident of ACP600 is analyzed and studied aiming at the disadvantageous situations that ACP600 cancels high pressure safety injection system and boron injection tank, using integrated gadolinium as burnable poison, adopting mode-Coperation and control mode and so on. For MSLB accident, because of the high peak power of the reactor core after re-reaching the critical state, in order to avoid the minimum DNBR(Departure from Nucleate Boiling Ratio) below the limiting value, the effects of different injection system configurations and tripping the fault loop’s reactor coolant pump on mitigating MSLB accident are evaluated from the viewpoints of rapid injection of boron solution and reduction of core cooling rate, and the best mitigation scheme is studied, the design optimization advice about adding "steam line pressure low-3 " signal for shutting down the fault loop is put forward.