The mechanical and anisotropic elastic properties of Bi12SiO20 (BSO) were investigated using density functional theory (DFT) calculations and nanoindentation. The calculated and experimentally observed XRD patterns of the compound were reported and the crystal structure of the BSO was determined to be cubic with the lattice constant of a = 1.025 nm. The second-order elastic constants and related polycrystalline elastic moduli (e.g. shear modulus, Young's modulus, Poisson's ratio, linear compressibility and hardness) were calculated. The calculated elastic constants indicated that BSO is mechanically stable and exhibits anisotropic characteristics. Moreover, the directional dependencies of sound wave velocities were investigated in three dimensions. Pressure-dependent bulk modulus was plotted at temperatures between 0 and 800 K. Hardness and Young's modulus were also determined by performing nanoindentation experiments on (222) and (631) planes of the BSO single crystal. The analyses of the experimental nanoindentation data resulted in hardness and Young's modulus values of 7.2 and 97.0 GPa, respectively. The results of DFT and nanoindentation were discussed throughout the paper. The results of the present paper would provide valuable information on the mechanical behaviours of the BSO for the optoelectronic device applications.