Conventional Al–Ti–B and Al–Ti–C refiners fail to refine Al–Si casting alloys with high Si content due to the well-known “Si-poisoning” effect. Developing a novel grain refiner with superior grain refinement efficiency for Al–Si casting alloys is the research focus in recent years. In this work, a superior anti Si-poisoning α-Al grain refiner Al–2La–1B alloy with fine LaB6 particles was successfully fabricated via the aluminum melt reaction method. The microstructural evolution, grain refinement performance and refinement mechanisms of the Al–2La–1B alloy were comprehensively investigated based on the experiment results and first-principles calculations. The currently designed Al–2La–1B refiner presents supreme grain refinement efficiency on Al–Si casting alloys. The average grain size of Al–7Si alloy inoculated with 0.5% Al–2La–1B alloy can be refined to 67 ± 5 μm. The superior grain refinement performance can be attributed to the presence of fine LaB6 particles in the refiner. These particles are highly stable in Al–Si alloy melt and can directly act as the potent nucleation sites for α-Al due to the small lattice misfit and low interfacial energy. Moreover, the nucleation potency of the LaB6 particles will not be influenced by the solute Si element. Our work provides an effective strategy for designing a superior α-Al grain refiner for Al–Si casting alloys.