A biohybrid therapeutic system, consisting of responsive materials and living microorganisms with inter-cooperative effects, is designed and investigated for tumor treatment. In this biohybrid system, S2 O3 2- -intercalated CoFe layered double hydroxides (LDH) are integrated at the surface of Baker's yeasts. Under the tumor microenvironment, functional interactions between yeast and LDH are effectively triggered, resulting in S2 O3 2- release, H2 S production, and in-situ generation of highly catalytic agents. Meanwhile, the degradation of LDH in the tumor microenvironment induces the exposure of the surface antigen of yeast, leading to effective immune activation at the tumor site. By virtue of the inter-cooperative phenomena, this biohybrid system exhibits significant efficacy in tumor ablation and strong inhibition of recurrence. This study has potentially offered an alternative concept by utilizing the metabolism of living microorganisms and materials in exploring effective tumor therapeutics.