β-Mg2Si is a common intermetallic phase in commercial Al alloys, which can influence the precipitation of age-hardening phases and mechanical properties. In this work, β-Mg2Si dispersoid formed in a novel multi-components Al-Mg-Zn based crossover alloy during homogenization has been explored in detail. It is found that β-Mg2Si owns a rarely observed cube-cube orientation relationship (OR) of [001]β//[001]Al, (100)β//(100)Al with Al matrix, while a Si-terminated {100} interface layer can be identified. More strikingly, it is revealed that β-Mg2Si/Al-matrix interfaces acted as preferential segregation sites for Zr, Zn and Cu atoms, causing heterogeneous nucleation of Al3Zr and T-(Al,Zn,Cu)49Mg32 phases at the interfaces. Resultantly, the growth of β-Mg2Si could be slowed down with their transition from cube-cube to Kanno OR being hindered. The underlying mechanisms have been revealed by applying first principles calculations of segregation energies of solute atoms based on the atomistic interfacial configuration.