The toxicity, reactivity, and behavior of zinc oxide (ZnO) nanoparticles (NPs) released in the environment are highly dependent on environmental conditions. Myo-inositol hexakisphosphate (IHP), a common organic phosphate, may interact with NPs and generate new transformation products. In this study, the role of IHP in mediating the dissolution and transformation of ZnO NPs was investigated in the laboratory kinetic experiments using powder X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, (31)P nuclear magnetic resonance spectroscopy, high-resolution transmission electronic microscopy, and synchrotron-based extended X-ray absorption fine structure spectroscopy. The results indicate that IHP shows a dissolution-precipitation effect, which is different from citrate and EDTA that only enhances Zn dissolution. The enhanced dissolution and transformation of ZnO NPs by IHP (<0.5 h) is found to be strikingly faster than that induced by inorganic phosphate (Pi, > 3.0 h) at pH 7.0, and the reaction rate increases with decreasing pH and increasing IHP concentration. Multitechnique analyses reveal that interaction of ZnO NPs with IHP induces rapid transformation of ZnO NPs into zinc phytate complexes initially and poorly crystalline zinc phytate-like (Zn-IHP) phase finally. Additionally, ZnO NPs preferentially react with IHP and transform to Zn-IHP when Pi and IHP concurrently coexist in a system. Overall, results from this study contribute to an improved understanding of the role of organic phosphates (e.g., IHP) in the speciation and structural transformation of ZnO NPs, which can be leveraged for remediation of ZnO-polluted water and soils.