Abstract: Linear ion trap-time of flight mass spectrometer (LIT-TOFMS) is one of multi-stage tandem mass spectrometry with high detection efficiency, high resolving power and high sensitivity. The differential vacuum system is the foundation of LIT-TOFMS. Basing on the principle of differential vacuum system, this paper introduces the choice of materials, vacuum measurement elements and pumping system. By the calculation, the LIT-TOFMS vacuum system- four-stage differential vacuum system is successfully designed. Both the calculations and the experiment results can prove that this system could meet the requirements of LIT-TOFMS and realize the pressure transition from atmospheric pressure to 10-4Pa, which is a reliable guarantee for the research and development of LIT-TOFMS.