The work aims to design and optimize the structure of the large-scale precision instrument transport packaging box to improve the airtightness and pressure bearing capacity of the packaging box while controlling the overall weight of the packaging box. According to the demand of "gas protection and sealing" during the transportation of precision instruments, a packaging box structure combined with steel frame and glass fiber was designed. The finite element simulation was used to analyze and evaluate the design scheme, and finally the pressure test and airtightness test of packaging box were conducted. The maximum deformation of the packaging box under extreme working conditions was 4.82 mm. Based on the in-box temperature and atmospheric pressure compensation model established, the leakage rate of the packaging box was only 520.5 Pa/48 h. In conclusion, the packaging box structure combined with steel frame and glass fiber meets the pressure bearing and sealing requirements for the transportation of large-scale precision instruments, and provides a reference for the design and testing of large sealed containers.