Nanoplastics (NPs) have emerged as pervasive environmental contaminants, yet their role in colorectal cancer (CRC) pathogenesis remains poorly understood. Here, we demonstrate that chronic oral exposure to polystyrene nanoplastics (PS-NPs) promotes colorectal tumorigenesis in a murine azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC model through disruption of the gut microbiota–metabolite–immune axis. Mechanistically, PS-NPs accumulate predominantly in the colon and cause structural damage to intestinal epithelial microvilli. PS-NPs induce gut microbiota dysbiosis characterized by depletion of the beneficial bacterium Faecalibaculum rodentium (F. rodentium) and a consequent reduction in its protective metabolite, propionic acid. This metabolic perturbation attenuates Th17 cell differentiation and IL-17 A production, thereby impairing anti-tumor immunity. Clinically, we detected diverse microplastics in CRC patient tissues and blood. Collectively, our multi-omics and functional analyses delineate a mechanistic pathway linking environmental NPs exposure to colorectal carcinogenesis via the F. rodentium–propionic acid–Th17 cell axis, highlighting the gut microbiome and its metabolites as potential targets for intervention against pollution-associated cancer risks.