The influence of cooling conditions on the temperature field and macro-segregation of Cr element of TC6 alloy ingot was investigated by MeltFlow-VAR. In order to validate the agreement between the model and experiment results, a full-scale TC6 ingot has been prepared. The simulation results show that with increase of the heat transfer between ingot and crucible, the depth of molten pool and mushy zone of ingot becomes shallower, and the whole ingot is solidified in a bottom-up sequence, which leads to the reduction of the segregation range of Cr element. The experimental results show that the solidified macrostructure is composed of full-columnar grains by using the irregular crucible with reduced wall thickness, which is beneficial to reduce segregation and obtain high quality ingot.