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In this work, a cellular automaton model has been developed to simulate the microstructure evolution of U-Nb alloy during the solidification process. The preferential growth orientation, solute redistribution in both liquid and solid, solid/liquid interface solute conservation, interface curvature and the growth anisotropy were considered in the model. The model was applied to simulate the dendrite growth and Nb microsegregation behavior of U-5.5Nb alloy during solidification, and the predicted results showed a reasonable agreement with the experimental results. The effects of cooling rates on the solidification microstructure and composition distribution of U-5.5Nb were investigated by using the developed model. The results show that with the increase of the cooling rate, the average grain size decreases and the Nb microsegregation increases.