Abstract: Tumor blockade therapy is a promising penetration-independent antitumor modality through inhibiting the substance exchange between the tumor and surrounding microenvironments. However, the strategies of vessel-targeted blockade, construction of an artificial extracellular matrix, and so forth are limited by possible side effects, inadequate tumor obstruction, and short duration. Inspired by the biomineralization in living organisms, artificially induced biomineralization in the tumor tissues has been emerging as an unconventional therapeutic modality characterized by long duration and satisfying biocompatibility. On this basis, our group reacted alendronate (ALN) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-hydroxysuccinimide eater (DSPE-PEG-NHS) to synthesize DSPE-PEG-ALN, in which the DSPE group was able to insert into cytomembrane, and bisphosphonic group attracted positive ions, mainly calcium ion, to initiate the chain reaction of biomineral deposition. Ultimately, an intense physical barrier was constructed in the periphery of tumor tissue, leading to effective tumor inhibition. To realize selective biomineralization around the tumor tissue, we designed a polypeptide-based biomineralization-inducing nanoparticle (BINP) equipped with the tumor microenvironment-responsiveness. Because of the hydrophobicity of long aliphatic chains, they were assembled in the interior of nanostructures at normal physiological conditions, while tending to expose at acidic microenvironments to selectively insert in the tumor cytomembrane. Then BINP initiated a biomineralized layer right there to achieve effective suppression of osteosarcoma progression. The design and application of in situ biomineralization-inducing functional polymers provide promising alternatives for clinical malignancy therapy.