With different pure metal materials such as copper, silver, tungsten, vanadium, tantalum and molybdenum as filler metals , the experiments of laser welding of 304 stainless steel (304 SS) and niobium are carried out by using the preset interlayer method. The results show that, among all the filler metals to be selected, Cu and Ag as interlayer can be used to realize the connection between 304 SS and niobium. The joint strength with the former as interlayer is the highest which reaches up to 250 MPa, thus the optimum filler metal is Cu. The hindering effect of Cu interlayer on the formation of Fe2Nb increases with the increase of Cu interlayer thickness, and so does the strength of joints, but the Cu interlayer cannot be too thick.