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Cancer has posed an enormous challenge to human health. To enhance cancer therapy, researchers have constructed the polyprodrug which drug molecules and polymer backbone polymerize to form. In the repeating prodrug units of the polyprodrug, the free drug is connected to the polymer backbone via stimuli-responsive linkages. Polyprodrugs have garnered increasing interest in recent years, due to their promising potential for the protection of drugs, increased drug loading, and systematic release of drugs in reaction to particular triggers. Herein, we present contemporary developments in reduction, pH, hypoxia, reactive oxygen species (ROS), enzymes, and light-responsive polyprodrug within these several decades. We also present the multi-function of polyprodrug triggered by multi-stimulus, before discussing strategies to enhance the targeting, penetration, and uptake of the polyprodrug. Finally, the existing clinical application and prospects of the polyprodrug are proposed.