Ion beam mixing has been demonstrated to play a critical role in growing refractory silicide epitaxially on silicon for the first time. Epitaxial ZrSi2 has been successfully grown on (111) and (001) Si. Best epitaxy was obtained in samples irradiated by As+ with an ion range close to the original Zr/Si interface to a dose of 1×1016/cm2 followed by 1100 °C annealing. The breaking of metal–oxygen bonds, dissolution of native silicon dioxide, as well as dispersion of impurities present at the interface by ion beam are thought to be beneficial in inducing the epitaxial growth of ZrSi2 on Si. The orientation relationships between epitaxial ZrSi2 and Si were found to be ZrSi2//Si, (002)ZrSi2//(220)Si (with about 1° misorientation), ZrSi2//Si, and (130)ZrSi2//(111)Si. Hexagonal and square networks of interfacial dislocations were observed. They were identified to be of edge type with (1)/(6) 〈112〉 or 1/2 〈110〉 Burgers vectors. The average spacings were measured to be 140 and 800 Å correspondingly. The results represent the first successful attempt to grow orthorhombic structure refractory silicide epitaxially on silicon.