In spite of the tumor microenvironments responsive can-cer therapy based on Fenton reaction (i.e., chemodynamic therapy, CDT) has been attracted more attentions in recent years, the limited Fenton reaction efficiency is the important obstacle to further application in clinic. Herein, we synthesized novel FeO/MoS2 nanocomposites modi-fied by bovine serum albumin (FeO/MoS2-BSA) with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photo-thermal effect of -MoS2 nanosheets triggered by the second near-infrared (NIR Ⅱ) light. In the tumor microenvironments, the -MoS2 nanosheets not only can accelerate the conversion of -Fe3+ ions to -Fe2+ ions by -Mo4+ ions on their surface to improve Fenton reaction efficiency, but also endow FeO/MoS2-BSA with good photothermal performances for photother-mal-enhanced CDT and photothermal therapy (PTT). Consequently, ben-efiting from the synergetic-enhanced CDT/PTT, the tumors are eradicated completely in vivo. This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.