In this study, the impact of different surface treatment and degree of vacuum on the interface and mechanical properties of 304/Q345 stainless steel clad plate was investigated. The study indicated that more continuous or aggregated Al2O3 and Si-Mn composite oxides were formed at the interface after brush grinding. However, less inclusions such as Al2O3, MnS and Ca-Mg-Al-Si composite oxides were formed at the interface after pickling treatment. For the vacuum degrees of 10−2 Pa, 1 Pa and 105 Pa, the oxidation reaction became more intense with the decrease in vacuum degree. The interface inclusions were gradually changed from Al2O3 and Si-Mn complex oxides to oxide scale and MnCr2O4 spinel oxide. The interfacial bonding strength of stainless steel clad plate was improved with the increase in degree of vacuum. The bonding strength was 55 MPa at vacuum of 105 Pa, but it was 484 MPa at vacuum of 10−2 Pa, which is far greater than that of the national standard, and an excellent performance was obtained.