The plastic deformation behavior of mechanical alloying powder at different ball milling times, microstructure and mechanical properties of hot press sintering Nb-35Ti-6Al-5Cr-8V alloys were investigated using powder metallurgy method. The results show that the Nb-35Ti-6Al-5Cr-8V powders with good plasticity were deformed into large-sized flakes powder firstly, and then broken into flocculent powder during continues process hardening as the increasing of ball milling time. The Nb-35Ti-6Al-5Cr-8V alloy with controllable microstructure and fine grain can be prepared using hot pressing sintering technology, and the sintered materials consist of single Nbss phase. The solid solution element of Ti, Al, Cr and V dissolving into Nb crystal causes the reduction of lattice size about 0.0685 ?. The Vickers hardness and the compression strength at room-temperature were increased significantly for grain refinement caused by ball milling time increasing, and this trend was in accordance with the Hall-Petch law of hardness and strength for material. It can be firmed that multi-mechanical properties of Nb-35Ti-6Al-5Cr-8V alloy prepared by powder metallurgy technology are obviously better than these prepared by fusion casting method.