Particulate matter (PM) exposure has been associated with intestinal disorders. Therefore, there is an urgent need to understand the precise molecular mechanism involved and explore potential prevention strategies. In this study, inhaled PM is shown to activate inflammatory pathways in murine colon. In a panel study, it is found that ambient PM levels are significantly associated with elevated number of fecal white blood cells in healthy subjects. Acting as a promoter, PM exposure accelerates chemical carcinogenesis-induced colonic tumor formation in a murine model. Mechanistically, RNA-seq assays suggest activation of phosphoinositide 3-kinase (PI3K)/AKT cascades in chronically PM-exposed human colon mucosal epithelial cells. Ablation of up-stream driver fibroblast growth factor receptor 4 (FGFR4) effectively inhibits inflammation and neoplasia in PM-exposed murine colons. Notably, dietary curcumin supplement is shown to protect against PM-induced colonic injuries in mice. Collectively, these findings identify that PM exposure accelerates colonic tumorigenesis in a PI3K/AKT-dependent manner and suggests potential nutrient supplement for prevention.