Highly ordered mesoporous materials with a single-crystalline structure have attracted broad interest due to their wide applications from catalysis to energy conversion/storage, but constructing them with good controllability and high yields remains a highly daunting task. Herein, we construct a new class of three-dimensionally ordered mesoporous SnO 2 single crystals (3DOm-SnO 2 ) with well-defined facets and excellent mesopore tunability. Mechanism studies demonstrate that the silanol groups on ordered silica nanospheres (3DO-SiO 2 ) can induce the efficient heterogeneous crystallization of uniform SnO 2 single crystals in its periodic voids by following the hard and soft acid and base theory, affording a much higher yield of ∼96% for 3DOm-SnO 2 than that of its solid counterpart prepared in the absence of 3DO-SiO 2 (∼1.5%). Benefiting from its permanent ordered mesopores and favorable electronic structure, Pd-supported 3DOm-SnO 2 can efficiently catalyze the unprecedented sequential hydrogenation of 4-nitrophenylacetylene to produce 4-nitrostyrene, then 4-nitroethylbenzene, and finally 4-aminoethylbenzene. DFT calculations further reveal the favorable synergistic effect between Pd and 3DOm-SnO 2 via moderate electron transfer for realizing this sequential hydrogenation reaction. Our work underlines the crucial role of silanol groups in inducing the high-yield heterogeneous crystallization of 3DOm-SnO 2 , shedding light on the rational design and construction of various 3DO single crystals that are of great practical significance.