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In situ synchrotron angle-dispersive x-ray diffraction experiments on niobium powders have been conducted at pres-sures up to 61 GPa and room temperature using the diamond anvil cell technique. From the full width at half maximum of the measured diffraction lines, the yield strength was derived with the line-width analysis theory. The niobium powder sample was found to be compressed more packed firstly and then yielded at~14 GPa–18 GPa. Following an initial increase in the yield strength with pressure, an obvious decrease was observed occurring at~42 GPa–47 GPa accompanying with a typical pressure dependence above 47 GPa. The experimentally observed anomalous softening of the yield strength in niobium surprisingly follows the trend of the predicted unusual softening in the shear modulus by the recent theoretical investigations. The possible mechanisms, applicable to interpret the yield strength softening of materials at high pressure, were also discussed in detail.