A coupled thermodynamic model of inclusions precipitation and microsegregation of solute elements during solidification of heat-resistant steel containing cerium is achieved. Then the validation of this model is conducted through commercial test and physical simulation experiment at high temperature in laboratory. The effect of cerium adding, oxygen content and sulfur content on the inclusions behavior during solidification of 253MA steel is studied. The results are concluded as follows. As the increase of cerium adding, SiO2 and MnS disappear, and CeN begins to form during solidification. Ce2O3, SiO2 and MnS are formed as the oxygen content increases, and the latter two are precipitated during the solidification. As the sulfur content increases, Ce3S4 and MnS are formed while Ce2O3 disappears, and the precipitation temperature of Ce3S4 develops from liquid-solid area to above the liquidus. All the work will indicate the theoretical direction to solve nozzle clogging problem of heat-resistant steel containing rare earth elements.