In this study, we investigate the effect of oxide dispersion strengthening on mechanical properties by dispersion of nano-sized Ta2O5 particles in Mo-Si-B alloy. A Mo-Si-B core-shell powder consisting of two intermetallic compounds of Mo5SiB2 and Mo3Si as the core and nano-sized Mo solid solution surrounding intermetallic compounds was fabricated by chemical vapor transport. And Mo-Si-B core-shell powder with uniformly dispersed nano-sized Ta2O5 particles on the surface of a Mo solid solution shell was produced by a wet blending process with TaCl5 solution and heat treatment. Then, pressureless sintering was performed at 1400°C for 3 h under a H2 atmosphere. The hardness and fracture toughness of the Ta2O5-dispersed Mo-Si-B alloy were measured using Vickers hardness and 3-point bending tests, respectively. The Vickers hardness and fracture toughness of the fabricated Mo-Si-B-Ta2O5 alloy were more improved than that of the Mo-Si-B alloy fabricated using core-shell powder with no addition of Ta2O5 particles (Mo-Si-B alloy: 353 Hv, 13.5 MPa·√m, Mo-Si-B-Ta2O5 alloy: 509 Hv, 15.1 MPa·√m).