Abstract: Through microstructure observation and hardness test, single-pulse resistance spot welding technology was used to study microstructure characteristics and changing rules of 22MnB5/DP590 welded joints with unequal thickness under different welding time and welding current, and thermophysical parameters such as electrical resistivity and thermal conductivity of DP590 and 22MnB5 base metals were calculated by JMatPro software. The results showed that nugget zone of spot welded joints was composed of coarse lath martensite, and heat affected zone on both sides could be divided into coarse grain zone and fine grain zone according to the prior austenite grain size. When welding current was 8.5 kA and welding time was 160 ms, liquefaction cracks appeared in heat-affected zone on the side of 22MnB5. With the increase of welding time, diameter of nugget first increased and then decreased, indentation rate of base materials on both sides increased, indentation rate on 22MnB5 side was larger than that on DP590 side, and nugget shifted to DP590 side. As welding current increased, diameter of nugget increased, indentation of 22MnB5 and DP590 first increased and then remained unchanged, and nugget offset was improved. Microhardness of nugget zone and heat-affected zone was higher than that of base metal, and microhardness of 22MnB5 heat-affected zone was the highest.