Herein, the Cu6Sn5 coatings with principal crystal orientations were prepared on the Cu substrate using magnetron sputtering to inhibit the growth of interfacial intermetallic compounds (IMCs) in Sn-0.7Cu/Cu solder joint. The effect of sputtering parameter on the principal crystal orientation of Cu6Sn5 coating was researched firstly, followed by the investigation on the influence of Cu6Sn5 coating principal orientation on the interfacial IMCs growth kinetics. The influence mechanisms were studied using molecular dynamics simulations and first-principles calculations. The results revealed that the increasing sputtering power from 40 W to 60 W and 80 W can not only improve the bonding property between the prepared Cu6Sn5 coating and Cu substrate, but also promote the transformation of the coating principal orientation from (132) to (132)/(22-1) and (132)/(22-1)/(42-2). Moreover, the three prepared Cu6Sn5 coatings can inhibit IMC growth at SC07/Cu solder joint, and the Cu6Sn5 coatings with (132)/(22-1) and (132)/(22-1)/(42-2) principal orientations exhibit more significant inhibitory effects on IMC growth than that with (132) principal orientation. It can be proved in this work that the growth of interfacial IMCs in Sn-0.7Cu/Cu solder joint at aging stage is mainly caused by the diffusion of Cu from Cu substrate toward Cu6Sn5 phase. The difference in the growth behavior of IMCs can be attributed to the fact that when the Cu atoms diffuse across Cu6Sn5 (22-1) and Cu6Sn5 (42-2), the bonding strength between the Cu atom at the saddle point and its surrounding atoms is significantly larger than when diffusing across Cu6Sn5 (132), leading to the smaller diffusion coefficients and a slower interfacial IMCs growth rate.