Abstract: The research objects were two types of advanced high strength steels 610CFD with 150mm thickness. Based on the different chemical composition of Z-direction, studied the effect of microstructure uneven on welding joint heat input. SEM, EBSD and impact tests were employed to characterize the results. The results show that improving casting billet thickness and reducing contents of segregation elemental, C and Mn is effective to reduce the segregation degree of 1/2 position and avoid metallurgical defects, thereby changing macro segregation into micro segregation; The obvious difference of 1/4 and 1/2 position heat affected zone (HAZ) microstructure resulting from serious macro segregation is the main reason why welding process adaptability on all positions along Z-direction have so much differences, while the mechanism that micro segregation leads to bad welding process adaptability is that the segregation of alloying elements causes the difference of MA's amounts, morphology and distribution in HAZ.