Atomic layer deposition of SiO2 using SiCl4 and H2O is a classical process, which was initially developed for applications in the field of microelectronics. Recently, it has been demonstrated as an effective surface engineering of nanomaterials in many other applications, including catalysis, pharmaceuticals, and energetic materials. However, fundamental mechanisms of SiO2 film growth at the atomic scale have not been fully understood. In this work, DFT calculations were performed to understand the atomic mechanisms of SiO2 film growth from SiCl4 and H2O precursors on the bare and hydroxylated TiO2 surfaces. Climbing image−nudged elastic band (CI-NEB) method was used to find saddle points and the activation energies for the chemical reactions of several possible mechanisms. The recombination of the by-product HCl with the surfaces and the removal of surface chlorine were also calculated. The results show that SiCl4 can be continuously dissociated on the surface or react with H2O after the first dissociation/ligand exchange reaction. The activation energies from CI-NEB results point out the benefit of the surface hydroxylation in facilitating the initial reaction of SiCl4 on the surface and reducing the production of the adsorbed atomic chlorine as gaseous HCl is released as a by-product. The recombination of the HCl by-product with the surface by either molecular dissociation or ligand exchange reaction with –OH groups can further create atomic chlorine. The removal of the adsorbed chlorine is unlikely, accounting for a certain amount of Cl impurity found by experiments. The calculation results provide an atomic level prediction for designing experimental conditions to achieve desired film quality.