As opposed to the common understanding that diffusion into a cubic-structured single crystal is independent of its crystalline orientation, the diffusion of Li to crystalline Si (c-Si) is anisotropic, which acts as the major cause for the fracture of Si anodes in Li-ion batteries. Here, by conducting comprehensive/multi-scale simulation studies based on molecular dynamics and density functional theory, we elucidate how and why Li diffusion in c-Si is anisotropic. We found that Li ions diffuse to c-Si by following a particular atomic-scale space corresponding to the lowest value of the valence orbital in c-Si, causing Li ions to take a tortuous diffusion pathway. The degree of the tortuosity of the pathway differs depending on the crystallographic orientation of Si, and it acts as the major cause for anisotropic lithiation. We also develop a structural parameter that can quantitatively evaluate the orientation dependency of the lithiation of c-Si.