Molecular adsorption on solids is inevitable and has significant influences on the wettability of materials, while the tuning mechanism of the wettability from molecular adsorption is yet to be understood. Using molecular dynamics (MD) simulations, we comprehensively studied the relation between the wettability of the TiO2 surface and the adsorption of water and carboxylic acid molecules. Our results reveal that the increasing amount of surface hydroxyl groups from the decomposition adsorption of H2O increases the hydrophilicity of TiO2, providing molecular-level evidence for the previously proposed mechanism of photo-induced hydrophilicity. By contrast, the surface wettability becomes tunable with water contact angles changing from 0 to ∼130° through length adjustment of the adsorbed carboxylic acids. The TiO2 surface is hydrophilic with the adsorption of short-alkyl-chain carboxylic acids (e.g., HCOOH) and becomes hydrophobic when longer-alkyl-chain carboxylic acids (H(CH2)nCOOH, n > 2) are present. Furthermore, long-alkyl-chain acids also increase surface oleophilicity, while the adsorption of HCOOH and CH3COOH significantly enhances the oleophobicity of TiO2. Water molecules can also more easily penetrate the space between oily contaminants and adsorbed short acid molecules, thereby further increasing its self-cleaning capacity. The present simulations not only reveal the mechanism of wettability caused by molecular adsorption but also provide a promising method to create materials with controllable wettability and high self-cleaning efficiency.