The as-cast Mg-6Al-2Ca-2Sm alloys were heat treated by solid solution and solid solution + aging treatment to obtain samples with different initial microstructure, and then hot extrusion was performed on samples with different initial microstructures. Effect of different initial microstructure on the microstructure and mechanical properties of hot-extruded Mg-6Al-2Ca-2Sm alloy was carried out by analyzing and testing. The results show that the Mg-6Al-2Ca-2Sm alloy undergoes obvious partial recrystallization after hot extrusion, and the grain is significantly refined; solid solution or solid solution + aging treatment can improve the distribution of metallic phases, and the precipitated phase distribution after hot extrusion is more uniform. The heat treatment before extrusion can improve the room temperature and high temperature mechanical properties of the hot extruded Mg-6Al-2Ca-2Sm alloy, and the solid solution + aging hot extruded alloy has the highest tensile strength and elongation.