Abstract: The method of AA-TIG welding to weld bottom and the submerged arc welding to fill the cover surface was used to study the butt welding of two large and thick plates of 12 Cr2 Mo1 R heat-resistant steel and 304 stainless steel. The microstructure and mechanical properties of welded joints were analyzed by methods of observing the microstructure and element distribution of welded joints and testing hardness, tensile properties, impact toughness and bending properties of welded joints. The results showed that the heat-affected zone of stainless steel was austenitic matrix with a small amount of band ferrite, the heat-affected zone of heat-resistant steel was bainite and martensite, while the weld was austenite and ferrite. It was founded by line scan analysis that the Fe and Ni element content in the fusion zone on the stainless steel side changed significantly, while the Fe, Ni, and Cr element content on the heat-resistant steel side change significantly. The microhardness test results showed that the hardness of the weld zone was about 220 HV, and there was obvious hardening in the heat-affected zone of heat-resistant steel. The tensile strength of welded joints was up to 678 MPa. The impact toughness of the weld and the heat-affected zone of stainless steel and heat-resistant steel at-30 ℃ was 132 J, 124 J, 241 J.