In this study, the synergistic effects of Y and Nd on the grain refinement of the as-cast Mg-Y-Nd-Al alloy was investigated by varying Y and Nd contents while fixing their total content (Y + Nd) at 7%. When the contents of Y and Nd were 3% and 4%, respectively, the refinement was most effective and the smallest grain size of 49±5 μm was achieved. The grain refinement process was primarily controlled by the heterogeneous nucleation and the growth restriction factor (Q value). Y could only form Al2RE phase with Al, while both Al2RE and Al11RE3 were formed between Nb and Al. The Al2RE phase acted as nucleation particles of α-Mg and facilitated heterogeneous nucleation; however, Al11RE3 was an unfavorable phase for heterogeneous nucleation. When the Y content was less than 3%, the quantity of Al2RE phase increased when more Y was available, which resulted in more active nucleation particles and better refinement. When the Y content exceeded 3%, the Q value (growth limiting factor) of the alloy decreased, while the quantity of Al2RE phase remained unchanged. This would lead to a decreased number of active nucleation particles and a less effective grain refinement.