The quick recombination of photogenerated carriers and the high surface reaction barrier are two important aspects influencing photocatalytic hydrogen generation. In this paper, a sulfur vacancy-modified twodimensional (2D) fluorinated-TiO 2 nanosheet/Mn 0.2 Cd 0.8 S (F-TiO 2 /MCS) Sscheme heterojunction was synthesized by a simple hydrothermal method to accelerate photogenerated electron transfer. The formation of an S-scheme heterojunction between MCS nanoflowers and 2D F-TiO 2 enhances the efficacy of photocatalytic hydrogen generation by facilitating the separation of photogenerated electron−hole pairs. Meanwhile, the sulfur vacancies of F-TiO 2 /MCS change the local electronic structure of the heterojunction surface by capturing photogenerated electrons, resulting in a photocatalytic hydrogen evolution rate for F-TiO 2 /MCS of 3197 μmol g −1 h −1 , which is 4.42 times greater than that of the pure MCS. Experimental measurements and density functional theory (DFT) calculations show that the mutual synergy between the S-scheme heterojunction and the sulfur vacancies not only provides abundant H 2 adsorption active sites but also promotes interfacial charge separation and migration, which improves the photocatalytic performance of the F-TiO 2 /MCS composite. This work holds significance for the photocatalytic hydrogen production of sulfur vacancy-modified S-scheme heterojunctions.