In this paper, we study the non-degenerate holomorphic $S^2$ in the complex Grassmann manifold $G(k,n), 2k\leq n$, by the method of moving frame. For a non-degenerate holomorphic one, there exists globally defined positive functions $\lambda_1,\ldots,\lambda_k$ on $S^2$. We first show that the holomorphic $S^2$ in $G(k, 2k)$ is totally geodesic if these $\,\lambda_i$ are all equal. Conversely, for any totally geodesic immersion 𝑓 from $S^2$ into $G(k, n)$, we prove that $f(S^2)\subset G(k, 2k)$ up to $U(n)$-transformation, $\lambda_i=\frac{1}{\sqrt{k}}$, the Gaussian curvature $K=\frac{4}{k}$ and 𝑓 is given by $(z_0,z_1)\mapsto(z_0 I_k,z_1 I_k,0)$, in terms of homogeneous coordinate.