Integration of microorganisms with semiconductors is an effective approach to sustainable solar-driven production of chemicals from CO2, which lies in the development of efficient, highly biocompatible, and low-cost photocatalysts. Herein, twinning Cd0.8Zn0.2S nanoparticles with long-range ordered homojunctions were synthesized and used for the first time in the construction of a biohybrid system (Cd0.8Zn0.2S/S. ovata) with a non-photosynthetic acetogenic bacterium of Sporomusa ovata. The Cd0.8Zn0.2S/S. ovata system yielded 49.33 ± 3.54 mM of acetate at a production rate of 8.22 ± 0.59 mM d−1 with a quantum efficiency of 16.82 ± 1.21% under illumination, which exceeded those of other reported biotic-abiotic hybrid systems. Further investigations revealed that the twin-induced homojunctions with staggered phase alignment contributed to enhance the separation efficiency of photogenerated electron-hole pairs and avoid photocorrosion of the photocatalyst. Due to the dual advantages of light absorption and biocompatibility of Cd0.8Zn0.2S, the Cd0.8Zn0.2S/S. ovata system could efficiently harvest light energy and transfer photogenerated electrons to cellular metabolism, driving the Wood-Ljungdahl pathway to efficiently synthesize acetate from CO2 under illumination.