Human NUDT16, a decapping enzyme belonging to the Nudix superfamily, plays a pivotal role in U8 snoRNA stability. Recombinant NUDT16 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals, which diffracted to 2.10 A resolution, belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 44.47, b = 79.32, c = 97.20 A. The Matthews coefficient and the solvent content were calculated to be 1.92 A(3) Da(-1) and 35.84%, respectively, for two molecules per asymmetric unit.