Two-dimensional niobium oxide diiodide (NbOI2) has recently attracted extensive attention due to its highly anisotropic band structures and rich physical characteristics in electronics and optoelectronics. Nevertheless, mechanical properties of NbOI2 have not been systematically investigated, which are critical parameters for applications. Here, we determine the directional dependence of Young's modulus of thin NbOI2 flakes by using an atomic force microscopy-based nanoindentation technique. We find that Young's moduli along two perpendicular in-plane crystalline axis, the c-axis and the a-axis, were 97.27 ± 2.12 and 51.51 ± 8.21 GPa, respectively. The anisotropic ratio is up to 1.89, which is a high anisotropy value in two-dimensional materials reported so far.