Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy. In addition, application of single mode drug usually leads to unsatisfactory therapeutic outcomes. Currently, developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge. Here, we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating cancer with minimal systemic toxicity. We demonstrated that this system can not only eliminate tumor cells