In this work, a series of subphthalocyanines (SubPcs) with a carboxylic acid anchoring group at the axial position were used as photosensitizers of TiO2 for photocatalytic hydrogen evolution from water under visible light irradiation. SubPc derivatives with various peripheral substituents were successfully prepared to systematically investigate the dependence of photocatalytic performance on electron-donating units (i.e., bisthiophene or thioether) at the peripheral position of the SubPcs. SubPc 2/TiO2/Pt shows the best photocatalytic activity among the three dye-sensitized photocatalysts, with a hydrogen evolution rate of 1.104 mmol·g-1·h-1. After 24 h irradiation, SubPc 2/TiO2/Pt achieved a remarkable catalytic activity for the production of H2 (19.96 mmol·g-1) with a TON value of 40 734 and a high STH efficiency of 2.1%. Density functional theory (DFT) and time-dependent DFT (TD-DFT) approaches were used to elucidate further structural and electrical properties, including the interaction patterns of tailored SubPcs. It is worth noting that the theoretical computations exhibit good conformity with the empirical data. The predicted fluctuations in photocatalytic activity detected in SubPc systems were shown to be closely associated with frontier molecular orbital (FMO) characteristics, noncovalent interaction (NCI) patterns, and the electron-donating nature of the fragments located at the peripheral positions.