Fiber laser welding process of Nb521 (Nb-5W-2Mo-1Zr) niobium alloy was studied. The effect of different process parameters on the weld forming and macroscopic morphology was studied. The microstructure and mechanical properties of the welded joint were analyzed. The welding powerwas kept constant at 6 kW, and the welding speed and defocuing were changed respectively. The results show that with the increase of the welding speed, the collapse of the weld is improved, but the continuity of the weld is gradually worse. When the welding speed reaches a certain value, many discontinuous humps appear on the back of the weld. When defocusing is positive, the weld formation quality is poor. When defocusing is negative, the edge biting phenomenon of weld is improved. When the laser power is 6 kW, the welding speed is 45 mm/s and the defocusing is -1 mm, showing that the weld is well formed. Under the optimized process parameters, the weld is a coarse columnar grain structure perpendicular to the fusion line, and the base metal is a fine equiaxed grain structure. The average tensile strength of the welded joints is 481 MPa at room temperature, which is equivalent to that of the base metal. The welded joints fracture in the heat-affected zone and the base metal respectively, and all of them are ductile fractures. The microhardness of weld is higher than that of base metal and heat-affected zone. In the top and bottom part of the welded joint, the microhardness of the heat affected zone softened and is lower than that of the base metal. The microhardness of the middle heat affected zone of the welded joint is similar to that of the base metal.