The insight into the rational design of nanostructure with complex functionality is a significant challenge for the advanced application of Zinc Oxide (ZnO) in various areas. Herein, heparin, as a biotemplate, was introduced to manipulate growth of ZnO nanoparticle into hierarchical structures with unusual morphology. The formation process of the morphology and microstructure of the as-achieved products were investigated. The heparin could alter nucleation and growth rates during the primary nanocrystal formation of ZnO, and promote the formation of two-dimensional nanoplates and subsequently self-assembly into novel quasi-microspherical ZnO superstructures with twinned donut-like hemispheres. The self-assembled quasi-microspheres displayed well crystallinity with a hexagonal wurtzite structure and a nearly uniform size-distribution with a value of 452.9 +/- 51.2 nm. The concentrations of heparin and zinc precursor played a vital role in determining the morphology of the resulting products. The possible growth mechanism of the obtained spherical like ZnO microparticles was proposed and discussed in detail. Our results are of fundamental importance to understanding crystal growth, and beneficial to promote the potential applications of ZnO with novel hierarchical structures in nanoscale devices.