Nb-16Si-22Ti-2Al-2Hf-2Cr bulk alloys have been prepared by powder metallurgy. The effects of milling time (5, 10, 20 h) of powder mixtures and hot-pressing temperatures (1500, 1600 °C) on the microstructure and room-temperature mechanical properties of the bulk alloys were investigated. It is revealed that the hot-pressed alloys are mainly composed of 3 phases including Nb solid solution (NbSS), Ti solid solution (TiSS) and Nb5Si3 silicides. With prolonging the milling time, the volume fractions of Nb5Si3 and TiSS phases increase, but that of NbSS phases decreases. The improvement in room-temperature hardness of bulk alloys is achieved with milling time and hot-pressing temperature increasing, and the bulk alloy milled for 20 h and hot-pressed at 1600 °C has the highest hardness of 11500 MPa. Moreover, the fracture toughness of the alloys hot-pressed at 1500 °C and 1600 °C both decreased with milling time prolonging. The bulk alloy milled for 5 h and hot-pressed at 1500 °C has the highest fracture toughness of 10.14 MPa·m1/2.