We report a 3.6 nm Ti-52-oxo cluster with precise atomic structure, which presents a largest size record in the family of titanium oxo clusters (TOCs). The crystal growth of such large Ti-52 is based on a stepwise interlayer assembly approach from Ti-6 substructures. The possible growth mechanism of Ti-52 could be deduced from crystal structures of two substructures, Ti-6 and Tim which were also synthesized under similar conditions as Ti-52. Moreover, these TOCs show cluster-size-dependent photo catalytic hydrogen evolution activities with Ti-52 giving a H-2 production rate up to 398 mu mol/h/g, which is also the highest record in the family of TOCs. This work not only represents a milestone in constructing large TOCs with comparable sizes as TiO2 nanoparticles but also brings significant advances in improving photo catalytic behaviors of TOCs.